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Article in Chinese | WPRIM | ID: wpr-981883


Objective To investigate the neuroprotective effect of methylene blue on diabetic retinopathy in rats. Methods Thirty SD rats were randomly divided into blank, control and experimental groups. The control and experimental groups were induced with diabetes by streptozotocin (STZ) intraperitoneal injection. After 6 weeks of successful modeling, the experimental group received intravitreal injection of methylene blue at a dose of [0.2 mg/(kg.d)], while the control group received an equal amount of dimethyl sulfoxide (DMSO) intravitreal injection, both continuously injected for 7 days. ELISA was used to detect the levels of retinal superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (iPF2α) and interleukin-1β (IL-1β) in rats. Western blot analysis was used to detect the expression of retinal extracellular signal-regulated kinase 1/2 phosphorylation (p-ERK1/2) and phosphorylated protein kinase B (p-AKT), and PAS staining was used to detect retinal morphological changes. Results Compared with the blank group rats, the retinal SOD activity in the control and experimental group rats was significantly reduced. iPF2α, IL-1β and p-ERK1/2 level increased, while p-AKT level decreased. Compared with the control group, the SOD activity of the experimental group rats increased. iPF2α and IL-1β level went down, while p-ERK1/2 and p-AKT level went up significantly. The overall thickness of the retinal layer and the number of retinal ganglion cells were significantly reduced. Conclusion Methylene blue improves diabetic retinopathy in rats by reducing retinal oxidative stress and enhancing ERK1/2 and AKT phosphorylation.

Rats , Animals , Diabetic Retinopathy/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Interleukin-1beta/metabolism , Methylene Blue/pharmacology , Phosphorylation , Rats, Sprague-Dawley , MAP Kinase Signaling System , Diabetes Mellitus, Experimental/drug therapy , Superoxide Dismutase/metabolism
Article in Chinese | WPRIM | ID: wpr-981391


This study investigated the effect of Lianmei Qiwu Decoction(LMQWD) on the improvement of cardiac autonomic nerve remodeling in the diabetic rat model induced by the high-fat diet and explored the underlying mechanism of LMQWD through the AMP-activated protein kinase(AMPK)/tropomyosin receptor kinase A(TrkA)/transient receptor potential melastatin 7(TRPM7) signaling pathway. The diabetic rats were randomly divided into a model group, an LMQWD group, an AMPK agonist group, an unloaded TRPM7 adenovirus group(TRPM7-N), an overexpressed TRPM7 adenovirus group(TRPM7), an LMQWD + unloaded TRPM7 adenovirus group(LMQWD+TRPM7-N), an LMQWD + overexpressed TRPM7 adenovirus group(LMQWD+TRPM7), and a TRPM7 channel inhibitor group(TRPM7 inhibitor). After four weeks of treatment, programmed electrical stimulation(PES) was employed to detect the arrhythmia susceptibility of rats. The myocardial cell structure and myocardial tissue fibrosis of myocardial and ganglion samples in diabetic rats were observed by hematoxylin-eosin(HE) staining and Masson staining. The immunohistochemistry, immunofluorescence, real-time quantitative polymerase chain reaction(RT-PCR), and Western blot were adopted to detect the distribution and expression of TRPM7, tyrosine hydroxylase(TH), choline acetyltransferase(ChAT), growth associated protein-43(GAP-43), nerve growth factor(NGF), p-AMPK/AMPK, and other genes and related neural markers. The results showed that LMQWD could significantly reduce the arrhythmia susceptibility and the degree of fibrosis in myocardial tissues, decrease the levels of TH, ChAT, and GAP-43 in the myocardium and ganglion, increase NGF, inhibit the expression of TRPM7, and up-regulate p-AMPK/AMPK and p-TrkA/TrkA levels. This study indicated that LMQWD could attenuate cardiac autonomic nerve remodeling in the diabetic state, and its mechanism was associated with the activation of AMPK, further phosphorylation of TrkA, and inhibition of TRPM7 expression.

Rats , Animals , AMP-Activated Protein Kinases/metabolism , Nerve Growth Factor/metabolism , Diabetes Mellitus, Experimental/drug therapy , TRPM Cation Channels/metabolism , GAP-43 Protein/metabolism , Signal Transduction , Diabetic Neuropathies/genetics , Fibrosis
Braz. j. biol ; 83: e247071, 2023. tab
Article in English | LILACS, VETINDEX | ID: biblio-1285609


Abstract The present study was conducted to evaluate the chemical composition, antioxidant activity and hypoglycemic effects of whole kumquat (Ku) powder in diabetic rats fed a high-fat-high-cholesterol (HFHC) diet. The antioxidant activities were evaluated using stable 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical scavenging method, 2,2´-azinobis (3-ethyl benzo thiazoline-6-sulphonic acid) radical cation (ABTS) and Ferric reducing antioxidant power (FRAP). Total phenolic content was (51.85 mg GAE/g) and total flavonoid content was (0.24 mg Cateachin Equivalent, CE/g). DPPH and ABTS values were 3.32 and 3.98 mg Trolox equivalent (TE)/g where FRAP value was 3.00 mM Fe2+/kg dry material. A total of 90 albino rats were used in the present study. Rats group were as follows: normal diet; normal treated (2, 4, and 6% Ku.), diabetic rats (non-treated), diabetic + HFHC diet (non-treated), HFHC (non-treated), Diabetic (treated), HFHC (treated) and Diabetic + HFHC (treated). The diets were followed for 8 weeks. Blood samples were collected at the end of the experiment. Serum glucose was recorded and thyroid hormones (T4, Thyroxine and T3, Triiodothyronine) were conducted. Diet supplemented with Kumquat at different concentrations have a hypoglycemic effect and improve the thyroid hormones of both diabetic rats and HFHC diabetic rats.

Resumo O presente estudo foi conduzido para avaliar a composição química, a atividade antioxidante e os efeitos hipoglicêmicos do pó de kumquat (Ku) em ratos diabéticos alimentados com uma dieta rica em gordura e colesterol (HFHC). As atividades antioxidantes foram avaliadas usando o método de eliminação de radicais livres de 1,1-difenil 2-picrilhidrazil (DPPH), 2,2'-azinobis (ácido 3-etilbenzotiazolina-6-sulfônico) radical cátion (ABTS) e antioxidante redutor férrico potência (FRAP). O conteúdo fenólico total foi (51,85 mg GAE / g) e o conteúdo total de flavonoides foi (0,24 mg Cateachin Equivalent, CE / g). Os valores de DPPH e ABTS foram 3,32 e 3,98 mg equivalente de Trolox (TE) / g, em que o valor de FRAP foi de 3,00 mM Fe2 + / kg de material seco. Um total de 90 ratos albinos foi usado ​​no presente estudo. O grupo dos ratos foi o seguinte: dieta normal: tratados normais (2, 4 e 6% Ku.), ratos diabéticos (não tratados), diabéticos + dieta HFHC (não tratados), HFHC (não tratados), diabéticos (tratados), HFHC (tratados) e diabéticos + HFHC (tratados). As dietas foram seguidas por 8 semanas. Amostras de sangue foram coletadas ao final do experimento. A glicose sérica foi registrada e os hormônios tireoidianos (T4, Tiroxina e T3, Triiodotironina) foram conduzidos. A dieta suplementada com kumquat em diferentes concentrações tem um efeito hipoglicêmico e melhora os hormônios tireoidianos tanto de ratos diabéticos quanto de ratos diabéticos com HFHC.

Animals , Rats , Rutaceae , Diabetes Mellitus, Experimental/drug therapy , Powders , Thyroid Hormones , Blood Glucose , Fruit
Article in English | WPRIM | ID: wpr-922565


OBJECTIVE@#To explore the effect of Tangshen Formula (, TSF), a Chinese herbal medicine, on interstitial cells of Cajal (ICC) in the colon of diabetic rats.@*METHODS@#Fifty-four male Wistar rats were randomly divided into normal control (NC, n=14) and high-fat diet (HFD) groups (n=40). After 6 weeks, the rats in the HFD group were injected intraperitoneally streptozotocin once (30 mg/kg). Thirty rats with fasting blood glucose higher than 11.7 mmol/L were randomly divided into diabetes (DM) and TSF groups, 15 rats in each group. Rats in the NC and DM groups were intragastrically administered with saline, and those in the TSF group were given with TSF (2.4 g/kg) once daily for 20 weeks. Expression levels of Bax, Bcl-2, and caspase-3 in colonic smooth muscle layer were measured by Western blotting and immunohistochemical staining. The number of ICC was determined by immunohistochemical staining. Immunofluorescence was used for analyzing the ratio of classically activated macrophages (M1) and alternatively activated macrophages (M2) to total macrophages. Electron microscopy was used to observe the epithelial ultrastructure and junctions.@*RESULTS@#TSF appeared to partially prevented loss of ICC in DM rats (P<0.05). Compared with the NC group, expression levels of Bcl-2, Bax, caspase-3, and TNF-α as well as the ratio of M1 to total macrophages increased in DM rats (all P<0.05), and the ratio of M2 to total macrophages decreased (P<0.05 or P<0.01). Compared with the DM group, TSF decreased the expression levels of abovementioned proteins and restore M2 to total macrophages ratio (P<0.05 or P<0.01). TSF appeared to attenuate the ultrastructural changes of epithelia and improve the tight and desmosome junctions between epithelia reduced in the DM rats.@*CONCLUSION@#Reduced number of ICC in DM rats may be associated with damage of the intestinal barrier. The protective effects of TSF on ICC may be through repair of the epithelial junctions, which attenuates inflammation and inflammation-initiated apoptosis in colon of DM rats.

Animals , Male , Rats , Colon , Diabetes Mellitus, Experimental/drug therapy , Drugs, Chinese Herbal/therapeutic use , Interstitial Cells of Cajal , Rats, Wistar
Braz. j. biol ; 82: e239378, 2022. graf
Article in English | LILACS, VETINDEX | ID: biblio-1249274


The genus Pouteria has been studied because it presents various activities, among which is its anti-inflammatory potential. The effects of Pouteria ramiflora Carbopol gel on the healing of skin wounds in diabetic rats were evaluated by microscopic imaging. Streptozotocin was administered intraperitoneally in animals that had fasted for 12 hours, a situation confirmed by the glycemic index (> 240 mg dL-1). An excision on the back of the animals was performed and three groups were formed: Control (Gel), Ethanolic extract (Ext) and Gel + extract 2% (Ext+gel); the histopathological evaluation occurred on the 7th, 14th, 21st and 30th days after the post-operative period. The results of the phytochemical prospecting of P. ramiflora extract demonstrated the major presence of phenolic compounds and flavonoids; the assessment of the inflammatory infiltrate on the 7th day was higher on group Ext and Ext+gel when compared to group Control; on the 14th day control and Ext (p<0.05). The quantification of fibroblasts was higher on the 7th day among the three treatments, control and Ext (p<0.05), on the 21st day. Angiogenesis showed a higher number of vessels in Ext+gel group (p<0.05) on the 7th day; in Control, Ext and Ext+gel (p<0.05) on the 14th day; and Control and Ext (p<0.05)on the 21st day. The histopathological results showed that the formulation Ext+gel was efficient in tissue reparation and decrease in inflammatory cells on the diabetic's animals.

O gênero Pouteria apresenta várias aplicações terapêuticas e, dentre elas, grande potencial antiflamatório. Os efeitos do gel de Pouteria ramiflora sobre a cicatrização de feridas na pele de ratos diabéticos foram avaliados pela histomorfometria. A estreptozotocina foi administrada por via intraperitoneal em animais após jejum de 12 horas, a confirmação de indução da diabetes foi confirmada pelo índice glicêmico (> 240 mg dL-1). Foi realizada uma incisão no dorso do animal e foram criados 3 grupos de tratamento: controle (gel carbopol), extrato etanólico (Ext) e Gel + extrato etanólico à 2% (Ext+gel); a avaliação histopatológica foi realizada no 7º, 14º, 21º e 30º dias após o período pós operatório. Os resultados da prospecção fitoquímica dos extratos de P. ramiflora demonstraram majoritariamente a presença de compostos fenólicos e flavonóides; o infiltrado inflamatório avaliado no 7º dia foi maior para animais do grupo controle em relação aos grupos Ext (p<0.05) e Ext+gel 2% (p<0.05); no 14º dia o controle e Exp (p<0.05) apresentaram aumento significativo dos infiltrados inflamatórios. A presença de fibroblastos foi elevada no 7º dia em todos os tratamentos. O processo da angiogênese mostrou um maior número de vasos sanguíneos entre os grupos Ext e Ext+gel (p<0.05) no 7º dia; no 14º dia o grupo controle, Ext (p<0.05), Control e Ext+gel (p<0.05) apresentaram aumento de vascularização, e no 21º dia apenas os grupos controle e Ext (p<0.05). Os resultados histopatológicos mostraram que a formulação gel carbopol + extrato etanólico a 2% foi eficiente na reparação de tecidos e na diminuição de células inflamatórias nos animais diabéticos.

Animals , Rats , Pouteria , Diabetes Mellitus, Experimental/drug therapy , Wound Healing , Flavonoids , Plant Extracts/therapeutic use , Plant Extracts/pharmacology
Arq. bras. cardiol ; 117(4): 715-725, Oct. 2021. tab, graf
Article in Portuguese | LILACS | ID: biblio-1345249


Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

Animals , Mice , Receptors, Chemokine , Diabetes Mellitus, Experimental/drug therapy , Carnitine/pharmacology , Chemokines , Intercellular Signaling Peptides and Proteins , Mice, Obese , Obesity/drug therapy
Electron. j. biotechnol ; 53: 87-94, Sep.2021. graf, ilus, tab
Article in English | LILACS | ID: biblio-1451559


BACKGROUND Diabetes is a metabolic disorder caused by defects in insulin production and activity. During disease progression, changes in lipid peroxidation cause structural modifications via production of free radicals. Fangchinoline is a well-known alkaloid present in Stephaniae tetrandrine S. Moore, which has demonstrated antioxidant, anticancer, and anti-inflammatory activities. RESULTS The present study analyzed the anti-diabetic and antioxidant effects of fangchinoline in male rats with streptozotocin-induced diabetes. Rats were divided into the following groups: normal control, diabetic, diabetic + fangchinoline 100 mg/kg, diabetic + fangchinoline 200 mg/kg and diabetic + glibencla mide 600 mg/kg. The treatment was administered orally for 45 consecutive days. Lipid peroxidation was substantially increased by >50% in the serum, as well as the liver, kidney, and heart tissues of diabetic rats. However, fangchinoline supplementation significantly reduced lipid peroxidation to near normal levels. Reactive oxygen species levels were substantially increased by >500% in the serum, as well as the liver, kidney, and heart tissues of diabetic rats. Fangchinoline supplementation reduced reactive oxygen species to near normal levels. Fangchinoline supplementation significantly improved superoxide dismutase, glutathione peroxidase, catalase, and reduced glutathione levels in diabetic rats. Total hexoses, sialic acid, hexosamines, and fucose were increased in diabetic rats, whereas fangchinoline supplementation significantly reduced these total hexoses, sialic acid, hexosamines, and fucose to near normal levels CONCLUSIONS Supplementation with fangchinoline led to significant attenuation of the levels of lipid peroxidation, ROS, and glycoprotein components such as total hexoses, hexosamines, sialic acid, and fucose, while improving antioxidant marker levels

Animals , Male , Rats , Benzylisoquinolines/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Reactive Oxygen Species , Streptozocin
Int. j. morphol ; 39(2): 577-586, abr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1385375


SUMMARY: Diabetes mellitus can lead to structural disorders in the brain. One of the most common complications of diabetes, diabetic neuropathy is associated with central nervous system disorders. Aloe vera has anti-diabetic, antioxidant, and neuroprotective effects. This study was designed to evaluate the effects of Aloe vera gel on the hippocampus changes as well as the expression of nerve growth factor and receptors TrkA and P75 in the hippocampus of streptozotocin (STZ)-induced diabetic rats. 25 male Wistar rats were randomly divided into 5 groups including: control (normal saline), diabetic (normal saline), Aloe vera gel (400 mg/kg/day; gavage), diabetic + Aloe vera gel (400 mg/kg/day; gavage) and diabetic + insulin NPH (10 IU/kg/day; subcutaneous). Experimental diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneal). All groups treated for 8 weeks. At the end of treatment course, the rat brains were removed for measuring the expression of nerve growth factor, p75 and TrkA receptors were evaluated in the hippocampus. Diabetes induction after 8 weeks caused NGF and P75 expression levels in the diabetic group than other groups significantly increased (p<0.05). The TrkA receptor expression in the diabetic group compared with the control had a significant reduction (p<0.05). On the other hand in the diabetic group receiving Aloe vera gel expression of NGF and P75 expression levels compared to the diabetic group was significantly reduced (p<0.05) and the TrkA receptor expression compared with the diabetic group had a significant increase (p<0.05). The results showed that oral administration of Aloe vera gel in diabetic rats ameliorates diabetes-induced hyperglycemia. On the other hand, Aloe vera gel cause modulation of the expression of NGF neurotrophic factor via increased expression of TrkA receptor-specific and non-specific receptor down-regulation of P75 in the hippocampus of STZ-induced diabetic rats.

RESUMEN: La diabetes mellitus puede provocar trastornos estructurales en el cerebro. Es una de las complicaciones más comunes de la diabetes y la neuropatía diabética y está relacionada con trastornos del sistema nervioso central. El Aloe vera tiene efectos antidiabéticos, antioxidantes y neuroprotectores. Este estudio fue diseñado para evaluar los efectos del gel de Aloe vera en los cambios del hipocampo, así como la expresión del factor de crecimiento nervioso y los receptores TrkA y P75 en el hipocampo de ratas diabéticas inducidas por estreptozotocina (STZ). Se dividieron al azar 25 ratas Wistar macho en 5 grupos de: control (solución salina normal), diabéticos (solución salina normal), gel de Aloe vera (400 mg / kg / día; sonda), diabéticos + gel de Aloe vera (400 mg / kg / día; sonda) y diabéticos + insulina NPH (10 UI / kg / día; subcutánea). La diabetes experimental fue inducida por inyección de estreptozotocina (60 mg / kg; intraperitoneal). Todos los grupos fueron tratados durante 8 semanas. Al final del tratamiento, se extrajeron los cerebros de las ratas para medir la expresión del factor de crecimiento nervioso y se evaluaron los receptores p75 y TrkA en el hipocampo. La inducción de diabetes después de 8 semanas provocó que los niveles de expresión de NGF y P75 en el grupo de diabéticos aumentaran significativamente en comparación con otros grupos (p <0,05). La expresión del receptor TrkA en el grupo diabético comparado con el control tuvo una reducción significativa (p <0,05). Por otro lado, el grupo de ratas diabéticas que recibieron la expresión en gel de Aloe vera de NGF y los niveles de expresión de P75 en comparación con el grupo de ratas diabéticas se redujo significativamente (p <0,05) y la expresión del receptor de TrkA en comparación con el grupo de ratas diabéticas tuvo un aumento significativo (p <0,05). Los resultados mostraron que la administración oral de gel de Aloe vera en ratas diabéticas mejora la hiperglucemia inducida por la diabetes. Por otro lado, el gel de Aloe vera causa modulación de la expresión del factor neurotrófico NGF a través del aumento de la expresión de receptor TrkA específico y no específico y regulación negativa del receptor de P75 en el hipocampo de ratas diabéticas inducidas por STZ.

Animals , Male , Rats , Plant Extracts/administration & dosage , Nerve Growth Factor/drug effects , Diabetes Mellitus, Experimental/drug therapy , Aloe/chemistry , Hippocampus/drug effects , Plant Extracts/pharmacology , Administration, Oral , Rats, Wistar , Receptor Protein-Tyrosine Kinases/drug effects , Receptor Protein-Tyrosine Kinases/genetics , Nerve Growth Factor/genetics , Receptor, Nerve Growth Factor/drug effects , Receptor, Nerve Growth Factor/genetics , Real-Time Polymerase Chain Reaction
Article in Chinese | WPRIM | ID: wpr-921747


This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.

Animals , Mice , AMP-Activated Protein Kinases/genetics , Diabetes Mellitus, Experimental/drug therapy , Diet, High-Fat/adverse effects , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts , Rehmannia , Signal Transduction , Streptozocin
Article in Chinese | WPRIM | ID: wpr-878991


This study aimed to explore the effect of Salviae Miltiorrhizae Radix et Rhizoma, its stems and leaves on the diversity of intestinal microflora in rats with diabetic kidney injury. Diabetic rats model was established by feeding high glucose and high fat diet and 5% glucose solution with intraperitoneal injection of 30 mg·kg~(-1) streptozocin(STZ). The rats were randomly divided into normal group, model group, irbesartan control group, Huangkui Capsules control group, as well as low, middle and high dose groups of Sal-viae Miltiorrhizae Radix et Rhizoma, its stems and leaves. After administration for 2 weeks, 16 S rRNA technique was used to analyze the diversity of intestinal microflora in the feces of each group. The results showed rats in the model group developed renal tubular epithelial vacuole degeneration and a large amount of inflammatory cell infiltration in the renal interstitium. A small amount of inflammatory cell infiltration was seen in each administration group. The kidney structure of rats in irbesartan group, Huangkui Capsules group, high-dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem water extract, as well as high dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem ethnol extract group was close to the normal group. The diversity and structure of intestinal flora in the model group were significantly different from those in the normal group. Each administration group improved the fecal flora diversity in rats with diabetic kidney injury to a certain extent, especially the high dose of Salviae Miltiorrhizae Radix et Rhizoma and its stems water extract. Different flora were found in feces of diabetic nephropathy model rats on class, order, family and genus levels. On families and genera levels, the relative abundance of Bifidobacterium, Turicibacter, Peptostreptococcaceae, Desulfovibrio, and SMB53 showed an upward trend in model group, but that of Lactobacillus, Clostridium, Rikenella, Rumen fungi showed a downward trend. The administration groups can improve the relative abundance of the above intestinal flora in the model rats to a normal-like level. The results of this study provide a reference for resource utilization and further development of Salviae Miltiorrhizae Radix et Rhizoma.

Animals , Rats , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Salvia miltiorrhiza
Article in Chinese | WPRIM | ID: wpr-888150


This study focused on the ameliorative effects of gypenosides(GPS) on insulin sensitivity and inflammatory factors in rats with type 2 diabetes mellitus(T2 DM) and explored their possible molecular mechanisms. After the successful establishment of T2 DM model, diabetic rats were randomly divided into four groups, including model group, GPS groups(200, 100 mg·kg~(-1)) and metformin group(100 mg·kg~(-1)), with healthy rats serving as the control. After 6-week intragastric administration, fasting blood glucose(FBG) and oral glucose tolerance were examined. The levels of insulin, C-peptide, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and C-reactive protein(CRP) in serum were examined. Then the homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index(ISI) were calculated. The protein expression levels of phosphorylated insulin receptor substrate-1(p-IRS-1) and phosphorylated protein kinase B(p-Akt) in skeletal muscle were measured by Western blot, as well as those of phosphorylated inhibitor of nuclear factor-κB(NF-κB) kinase β(p-IKKβ), phosphorylated alpha inhibitor of NF-κB(p-IκBα) and phosphorylated p65 subunit of NF-κB(p-p65) in adipose tissue. The relative expression levels of glucose transporter 4(GLUT4) mRNA in skeletal muscle and NF-κB mRNA in adipose tissue were measured by qRT-PCR, and the morphological changes of pancreatic tissue were observed. Compared with the model group, the GPS groups witnessed significant decrease in FBG, marked amelioration of impaired oral glucose tolerance and significant increase in ISI. Further, the high-dose GPS group saw significantly reduced HOMA-IR, TNF-α, IL-1β and CRP, significantly increased expression levels of p-IRS-1(Tyr), p-Akt and GLUT4, and markedly inhibited p-IRS-1(Ser), p-IKKβ, p-IκBα, p-p65 and NF-κB. The concentration of CRP and the expression levels of p-IRS-1(Ser), p-IKKβ, p-IκBα and NF-κB were remarkably reduced in the low-dose GPS group. However, GPS was found less effective in the regulation of serum insulin, C-peptide and IL-6 levels and the alleviation of pancreatic islet injury. The results indicated that GPS can reduce FBG and improve insulin sensitivity in diabetic rats possibly by regulating the NF-κB signaling pathway, inhibiting inflammation, and thereby regulating the expression of key proteins in the insulin signaling pathway.

Animals , Rats , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/genetics , Gynostemma , Insulin , Insulin Resistance , NF-kappa B/metabolism , Plant Extracts , Signal Transduction
Article in English | WPRIM | ID: wpr-880354


BACKGROUND@#Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats.@*METHODS@#The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols.@*RESULTS@#HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide.@*CONCLUSION@#The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.

Animals , Male , Rats , 1-Butanol/chemistry , Administration, Oral , Diabetes Mellitus, Experimental/drug therapy , Dose-Response Relationship, Drug , Hypoglycemic Agents/chemistry , Periploca/chemistry , Phytochemicals/chemistry , Plant Extracts/chemistry , Rats, Sprague-Dawley , Streptozocin/adverse effects
Article in Chinese | WPRIM | ID: wpr-942248


OBJECTIVE@#To investigate the effects of topical administration of cyclosporine A (CsA) on salivary secretion and inflammation of the submandibular glands in non-obese diabetic (NOD) mice.@*METHODS@#Female NOD mice, 21 aged 14 weeks and 18 aged 21 weeks were selected and randomly divided into low-dose group, high-dose group and control group on average. CsA was injected into submandibular glands. One week later the saliva stimulated by pilocarpine was collected and measured. The submandibular glands were collected to make paraffin sections. The lymphocyte infiltration in submandi-bular gland was observed by microscope after hematoxylin-eosin (HE) staining. The number of lymphocyte infiltration foci was counted to calculate the focus sore and the ratio of lymphocyte infiltration area to total gland area was figured up by Leica image analysis system. The expressions of inflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-13, IL-17F, IL22 and IL-23a in the submandibular glands of the NOD mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis in the submandibular gland was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The levels of serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), alanine aminotransferase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB) and γ-glutamyl transferase (GGT) were measured by automatic biochemical analyzer to evaluate liver and kidney functions.@*RESULTS@#After topical injection of CsA in the submandibular gland, the stimulated salivary flow rate of the 14- and 21-week-old NOD mice significantly increased compared with the control group (P < 0.01 or P < 0.05), and the number and area of lymphocyte infiltration foci in the 14-week-old NOD mice low-dose group significantly decreased compared with the control group (P < 0.01). Low and high dose of CsA had similar effects on reducing inflammation and improving salivary secretion. The overall level of inflammatory cytokines in the submandibular gland did not decrease significantly. The number of cell apoptosis of submandibular gland in the NOD mice treated with CsA decreased compared with the control group, but there was no statistically significant difference. Topical injection of CsA had no adverse effect on liver and kidney function in the NOD mice.@*CONCLUSION@#Topical injection of CsA can reduce lymphocyte infiltration in submandibular gland of NOD mice and improve salivary secretion.

Animals , Female , Mice , Cyclosporine , Diabetes Mellitus, Experimental/drug therapy , Disease Models, Animal , Inflammation , Mice, Inbred NOD , Saliva , Sjogren's Syndrome , Submandibular Gland
Rev. bras. parasitol. vet ; 30(4): e012121, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1351871


Abstract The present work aims to investigate the antiparasitic and the immunomodulating effects of nitazoxanide (NTZ) and ivermectin (IVC) alone or combined together or combined with selenium (Se), on Cryptosporidium infection in diabetic mice. The results revealed that the combined NTZ and IVC therapy achieved the highest reduction of fecal oocysts (92%), whereas single NTZ showed the lowest reduction (63%). Also, adding Se to either NTZ or IVC resulted in elevation of oocyst reduction from 63% to 71% and from 82% to 84% respectively. All treatment regimens, with the exception of NTZ monotherapy, showed a significant improvement in the intestinal histopathology, the highest score was in combined NTZ and IVC therapy. The unique results of immunohistochemistry in this study showed reversal of the normal CD4/CD8 T cell ratio in the infected untreated mice, however, following therapy it reverts back to a normal balanced ratio. The combined (NTZ+ IVC) treatment demonstrated the highest level of CD4 T cell expression. Taken together, NTZ and IVC combined therapy showed remarkable anti-parasitic and immunostimulatory effects, specifically towards the CD4 population that seem to be promising in controlling cryptosporidiosis in diabetic individuals. Further research is required to explore other effective treatment strategies for those comorbid patients.

Resumo O presente trabalho tem como objetivo investigar os efeitos anti-parasitários e imunomodulantes da nitazoxanida (NTZ) e ivermectina (IVC), isoladas ou em associação, e do selênio (SE), associado à NTZ ou à IVC, sobre a infecção por Cryptosporidium em camundongos diabéticos. Os resultados revelaram que a terapia combinada com NTZ e IVC resultou em maior redução de oocistos fecais, enquanto a NTZ isolada mostrou a menor redução de oocistos fecais (63%). Além disso, a associação do SE com a NTZ ou IVC resultou em redução do número de oocistos fecais de 63% para 71% e de 82% para 84%, respectivamente. Todos os tratamentos, com exceção da monoterapia com NTZ, mostraram uma melhora significativa nos índices relacionados à histopatologia intestinal. Os resultados da imuno-histoquímica mostraram reversão da razão celular CD4/CD8 T normal nos camundongos infectados não tratados, no entanto, após a terapia, houve retorno à razão celular CD4/CD8 T normal. O tratamento combinado (NTZ+ IVC) demonstrou o mais alto nível de expressão celular CD4 T. Em conclusão, a terapia combinada com NTZ e IVC mostrou efeitos anti-parasitários e imunoestimuladores notáveis, especificamente para a população CD4, que parecem ser promissores para o controle da criptosporidiose em indivíduos diabéticos.

Animals , Rabbits , Rodent Diseases , Selenium/therapeutic use , Cryptosporidiosis/drug therapy , Cryptosporidium , Diabetes Mellitus, Experimental/drug therapy , Thiazoles , Ivermectin/therapeutic use , Nitro Compounds , Antiparasitic Agents/therapeutic use
Acta cir. bras ; 36(2): e360207, 2021. tab, graf
Article in English | LILACS | ID: biblio-1152700


ABSTRACT Purpose The present study explored the influence of liraglutide on remote preconditioning-mediated cardioprotection in diabetes mellitus along with the role of nuclear factor erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor (HIF-1α) and hydrogen sulfide (H2S). Methods Streptozotocin was given to rats to induce diabetes mellitus and rats were kept for eight weeks. Four cycles of ischemia and reperfusion were given to hind limb to induce remote preconditioning. After 24 h, hearts were isolated and subjected to 30 min of ischemia and 120 min of reperfusion on Langendorff system. Liraglutide was administered along with remote preconditioning. Cardiac injury was assessed by measuring the release of creatine kinase (CK-MB), cardiac troponin (cTnT) and development of left ventricular developed pressure. After ischemia-reperfusion, hearts were homogenized to measure the nuclear cytoplasmic ratio of Nrf2, H2S and HIF-1α levels. Results In diabetic rats, there was more pronounced injury and the cardioprotective effects of remote preconditioning were not observed. Administration of liraglutide restored the cardioprotective effects of remote preconditioning in a dose-dependent manner. Moreover, liraglutide increased the Nrf2, H2S and HIF-1α levels in remote preconditioning-subjected diabetic rats. Conclusions Liraglutide restores the lost cardioprotective effects of remote preconditioning in diabetes by increasing the expression of Nrf2, H2S and HIF-1α.

Animals , Rats , Myocardial Reperfusion Injury/prevention & control , Ischemic Preconditioning, Myocardial , Diabetes Mellitus, Experimental/drug therapy , Hydrogen Sulfide , Hydrogen Sulfide/pharmacology , Myocardial Infarction , Signal Transduction , Rats, Wistar , NF-E2-Related Factor 2 , Liraglutide/pharmacology
Bol. latinoam. Caribe plantas med. aromát ; 20(2): 132-146, 2021. ilus, tab
Article in English | LILACS | ID: biblio-1342208


We investigated the effects of dichloromethane extract (DME) from Myrcia splendenson alterations caused by type 2 diabetes in the blood and kidney of rats, in order to reduce side effects caused by synthetic drugs. Rats received streptozotocin (60 mg/kg),15 minutes after nicotinamide (120 mg/kg) or water. After 72 hours, the glycemic levels were evaluated to confirm diabetes and the animals received (15 days) DME (25, 50, 100 or 150 mg/Kg) or water. DME partially reversed hyperglycemia and (100 and 150 mg/kg) reversed hypertriglyceridemia. Histopathological findings elucidated that DME reduced damage to pancreatic islets. DME 150 mg/kgreversed the increases in TBA-RS, the reduction in the sulfhydryl content, 100 and 150 mg/kg increased CAT, reversed the decrease in GSH-Px and increased it activity in the blood. DME 150 mg/kg reversed CAT and GSH-Px reductions in the kidney. We believe that DME effects might be dependent on the presence of phenolic compounds.

Investigamos los efectos del extracto de diclorometano (DME)de Myrcia splendens sobre las alteraciones causadas por la diabetes tipo 2 en la sangre y los riñones de las ratas, para reducir los efectos secundarios causados por las drogas sintéticas. Las ratas recibieron estreptozotocina (60 mg/kg), 15 minutos después de la nicotinamida (120 mg/kg) o agua. Después de 72 horas, se confirmo la diabetes y los animales recibieron (15 días) DME (25, 50, 100 o 150 mg/Kg) o agua. DME revierte parcialmente la hiperglucemia y revierte la hipertrigliceridemia. DME redujo el daño a los islotes pancreáticos. DME revirtió los aumentos en TBA-RS, la reducción en el contenido de sulfhidrilo, aumentó la CAT, revirtió la disminución en GSH-Px y aumentó su actividad en la sangre. Además, DME revirtió las reducciones de CAT y GSH-Px en el riñón. Creemos que los efectos provocados por DME pueden depender de la presencia de compuestos fenólicos.

Animals , Male , Rats , Plant Extracts/administration & dosage , Myrtaceae/chemistry , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/administration & dosage , Methylene Chloride/administration & dosage , Blood Glucose/drug effects , Plant Extracts/chemistry , Chromatography, High Pressure Liquid , Rats, Wistar , Streptozocin , Oxidative Stress/drug effects , Spectrometry, Mass, Electrospray Ionization , Phenolic Compounds/analysis , Hypolipidemic Agents/administration & dosage , Antioxidants/administration & dosage
Int. j. morphol ; 38(6): 1693-1699, Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134500


SUMMARY: Herbal extracts used for treatment of diabetes has focused mostly on the hypoglycaemic and anti-oxidant property.There are no studies which focused on its effect on dendritic architecture of pyramidal neurons of hippocampus caused by diabetes. This study was taken up to explore the effect of administration of Trigonella foenum-graecum (fenugreek) seed extract on diabetes induced dendritic atrophy in hippocampus. Experimental diabetes was induced in rats by administering single dose of Streptozotocin (60 mg/kg)intraperitoneally.Treatment groups of rats were orally administeredfenugreek seed extract of 1 g/kg body weight for 6 weeks. Followingly they were sacrificed and the brains were removed, processed for the Golgi-Cox stain method.The number of dendritic branching points and intersections were counted in successive radial segments of 20 µm up to a radial distance of 100 micron from soma and analysed by the Sholl's method. The rats with diabetes showed a significant decrease in the dendritic length and branching points in most of the apical and basal dendrites of CA1 and CA3 pyramidal neurons.Treatment with fenugreek seed extract were able to significantly alleviate the dendritic atrophy in most of the segments except in the apical branching points of the CA1 neuron. The present study demonstrates that fenugreek seed extract having a proven hypoglycaemic and anti-diabetic property also possess protection to the hippocampal pyramidal neurons form diabetes associated neuronal atrophy.

RESUMEN: Los extractos de hierbas para el tratamiento de la diabetes se han basado principalmente en las propiedades hipoglucémicas y antioxidantes. En la literatura no hay estudios basados en su efecto sobre la arquitectura dendrítica de las neuronas piramidales del hipocampo, causadas por la diabetes. El objetivo de este estudio fue investigar el efecto de la administración de extracto de semilla de Trigonella foenum graecum (fenogreco) sobre la atrofia dendrítica inducida por la diabetes en el hipocampo. Se indujo diabetes experimental en ratas mediante la administración de una dosis única de estreptozotocina (60 mg / kg) por vía intraperitoneal. Se administró a grupos de ratas extracto de semilla de fenogreco a razón de 1 g / kg de peso corporal durante 6 semanas. Las ratas fueron sacrificadas posteriormente y se procesaron los cerebros mediante método de tinción de Golgi-Cox. El número de puntos de ramificación dendrítica e intersecciones se contaron en segmentos radiales sucesivos de 20 µm hasta una distancia radial de 100 micras del soma y se analizaron mediante el método de Sholl. Las ratas con diabetes mostraron una disminución significativa en la longitud dendrítica y los puntos de ramificación en la mayoría de las dendritas apicales y basales de las neuronas piramidales CA1 y CA3. El tratamiento con extracto de semilla de fenogreco alivió significativamente la atrofia dendrítica en la mayoría de los casos, excepto en los puntos de ramificación apical de la neurona CA1. El estudio demuestra que el extracto de semilla de fenogreco además de tener propiedades hipoglucémicas y antidiabéticas, también protege las neuronas piramidales del hipocampo contra la atrofia neuronal asociada a la diabetes.

Animals , Male , Rats , Atrophy/drug therapy , Plant Extracts/administration & dosage , Trigonella/chemistry , Dendrites/drug effects , Diabetes Mellitus, Experimental/drug therapy , Plant Extracts/therapeutic use , Rats, Wistar , Pyramidal Cells , Diabetes Mellitus, Experimental/complications , Hippocampus/drug effects
Int. j. morphol ; 38(5): 1330-1335, oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134444


SUMMARY: The aim of this study is to investigate the effects of Protocatechuic acid and Corchorus olitorius on streptozotocin (STZ) induced diabetic rat testis tissue. Randomly selected Wistar Albino rats were divided into five groups as; Diabetes Mellitus, Diabetes Mellitus treated with Corchorus Olitorus (STZ+CO), Diabetes Mellitus treated with Protacatechuic acid (STZ+PCA), Corchorus olitorius (CO), Protocatechuic acid (PCA) and Control. Diabetic model was generated by intraperitoneal injection of 60 mg/kg Streptozotosin. After 48 hours of the STZ injection, blood samples were collected from tail vein in order to measure blood glycose levels. Over 250 mg/dL accepted as diabetic subjets and fed with 250 mg/kg Corchorus olitorius or 20 mg/kg PCA by oral gavage for three weeks. At the end of the experiment, right testes were removed and fixed in 10 % neutral formaldehyde for paraffine embedding. Sections were stained by HE, Masson trichrome, PAS and TUNEL for microscopic evaluation. Control, PCA-only and Corchorus olitorius-only treated group testes tissues showed a normal tissue organization, when degeneration in seminiferous tubules, the vacuolization, seperations in spermatogenic cell series, outpouring of cell groups in the lumen, vesicular body formation, liquid accumulation in the interstitial region and edema were observed in STZ induced diabetic models and untreated groups. Besides, higher amount of TUNEL (+) stained cells were determined in STZ group. On the other hand, blood glucose level and number of TUNEL (+) stained cells were decreased as a result of PCA and Corchorus olitorius treatment. Because of the reduction of blood glucose level and apoptotic cell numbers, PCA and Corchorus olitorius decreace the complications of diabetes mellitus induced rat testis.

RESUMEN: El objetivo de este estudio fue investigar los efectos del ácido protocatéquico y Corchorus olitorius sobre el tejido testicular de rata diabética inducida por estreptozotocina (STZ). Las ratas Wistar Albino fueron seleccionadas al azar y se dividieron en cinco grupos; Diabetes Mellitus, Diabetes Mellitus tratada con Corchorus olitorius (STZ + CO), Diabetes Mellitus tratada con ácido protocatéquico (STZ + PCA), Corchorus olitorius (CO), ácido protocatéquico (PCA) y Control. El modelo diabético se generó por inyección intraperitoneal de 60 mg/kg de estreptozotosina. Después de 48 horas de la inyección de STZ, se recogieron muestras de sangre de la vena de la cola para medir los niveles de glucosa. Niveles mayores a 250 mg/dL fueron considerados como especímenes diabéticos y alimentados con Corchorus olitorius de 250 mg/kg o PCA de 20 mg/kg por sonda oral durante tres semanas. Al final del experimento, se extirparon los testículos derechos y se fijaron en formaldehído neutro al 10 % para la inclusión en parafina. Las secciones se tiñeron con HE, tricromo de Masson, PAS y TUNEL para evaluación microscópica. Los tejidos de los testículos de los grupos control, tratados solo con PCA y con Corchorus olitorius mostraron una organización tisular normal. En cambio en modelos diabéticos inducidos por STZ y grupos no tratados se observó degeneración en los túbulos seminíferos, vacuolización, separaciones en series de células espermatogénicas, efusión de grupos celulares en la luz, formación del cuerpo vesicular, acumulación de líquido en la región intersticial y edema. Además, se determinó una mayor cantidad de células teñidas con TUNEL (+) en el grupo STZ. Por otro lado, el nivel de glucosa en sangre y el número de células teñidas con TUNEL (+) disminuyeron como resultado del tratamiento con PCA y Corchorus olitorius. Debido a la reducción del nivel de glucosa en sangre y el número de células apoptóticas, se observó que PCA y Corchorus olitorius disminuyen las complicaciones de los testículos de rata inducidos por diabetes mellitus.

Animals , Male , Rats , Testis/drug effects , Plant Extracts/pharmacology , Corchorus/chemistry , Diabetes Mellitus, Experimental/drug therapy , Hydroxybenzoates/pharmacology , Seminiferous Tubules/drug effects , Blood Glucose/analysis , Plant Extracts/therapeutic use , Rats, Wistar , Hydroxybenzoates/therapeutic use
Int. j. morphol ; 38(4): 1003-1009, Aug. 2020. tab, graf
Article in English | LILACS | ID: biblio-1124889


This study was set to investigate the effect of gum Arabic (G.A.) on diabetic kidney disease. We divided sixty male Sprague rats randomly into six groups. Normal control, normal rats treated with G.A., untreated diabetic rats, diabetic rats treated with insulin, diabetic rats treated with G.A., and diabetic rats treated with both insulin and G.A. Diabetes was induced by a single intraperitoneal injection of STZ. Forty eight hr post injections. Insulin was injected subcutaneously (1.6/IU/100g/day). We provided G.A. in drinking water (10 %w/ v).). At the end of the twelve weeks, blood was drawn for measurement of blood glucose, glycosylated hemoglobin (HbA1C), serum lipids, serum creatinine, and blood urea. Renal tissue oxidative stress (O.S.) was assessed by measuring the activities of superoxide dismutase (SOD) and catalase (CAT), and the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA). For histological assessments, sections from segments of kidneys were processed and stained with hematoxylin and eosin (H&E) for assessment under the light microscope. STZinduced diabetes caused an elevation of blood glucose, HbA1c, urea and creatinine, triglycerides LDL and cholesterol, MDA with reduction of HDL, GSH level, and CAT and SOD activities. Histologically, kidneys from diabetic rats showed marked glomerular and tubular changes. Administration of G.A. alone to diabetic rats had a significant hypoglycemic, hypolipidemic, and antioxidant effect, although the levels achieved remained significantly abnormal compared with the untreated group with no effect on urea and creatinine levels. Co-administration of G.A. with insulin reversed the impact of D.M. on all parameters evaluated including the histological changes and led to normal urea and creatinine levels. We concluded that G.A., in combination with insulin, improves chemically-induced diabetes and its renal complications, possibly by modulation of oxidative stress.

En este estudio se evaluó el efecto de la goma arábiga (GA) en la enfermedad renal diabética. Dividimos sesenta ratas macho Sprague Dawley al azar en seis grupos. Control normal, ratas normales tratadas con GA, ratas diabéticas no tratadas, ratas diabéticas tratadas con insulina, ratas diabéticas tratadas con GA y ratas diabéticas tratadas con insulina y GA. La diabetes fue inducida por una sola inyección intraperitoneal de STZ. Cuarenta y ocho horas después se inyectó insulina por vía subcutánea (1,6 / UI / 100 g / día). A los animales se les dió GA en agua potable (10 % p / v)). Al final de las doce semanas, se extrajo sangre para medir la glucosa, la hemoglobina glicosilada (HbA1C), los lípidos en suero, la creatinina en suero y la urea en sangre. El estrés oxidativo del tejido renal (SO) se evaluó midiendo las actividades de la enzima superóxido dismutasa (SOD) y la catalasa (CAT), y las concentraciones de glutatión reducido (GSH) y malondialdehído (MDA). Para las evaluaciones histológicas, se procesaron secciones de segmentos de riñones y se tiñeron con hematoxilina y eosina (H & E) para análisis bajo microscopio óptico. La diabetes inducida por STZ causó una elevación de la glucosa en sangre, HbA1c, urea y creatinina, triglicéridos LDL y colesterol, MDA con reducción de las actividades de HDL, GSH y CAT y SOD. Histológicamente, los riñones de ratas diabéticas mostraron marcados cambios glomerulares y tubulares. La administración de GA solo en las ratas diabéticas tuvo un efecto hipoglucémico, hipolipidémico y antioxidante significativo, aunque los niveles alcanzados permanecieron significativamente anormales en comparación con el grupo no tratado, sin ningún efecto sobre los niveles de urea y creatinina. La dministración conjunta de GA con insulina revirtió el impacto de DM en todos los parámetros evaluados, incluidos los cambios histológicos y condujeron a niveles normales de urea y creatinina. Concluimos que GA en combinación con insulina, mejora la diabetes inducida químicamente y sus complicaciones renales, posiblemente mediante la modulación del estrés oxidativo.

Animals , Male , Rats , Diabetic Nephropathies/prevention & control , Gum Arabic/administration & dosage , Antioxidants/administration & dosage , Rats, Sprague-Dawley , Oxidative Stress/drug effects , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/pathology , Gum Arabic/pharmacology , Injections, Intraperitoneal , Kidney/drug effects , Antioxidants/pharmacology
Int. j. morphol ; 38(3): 627-633, June 2020. tab, graf
Article in English | LILACS | ID: biblio-1098298


Diabetes Mellitus (DM) is a condition marked by hyperglycaemia that causes systemic complications, including urinary vesicle dysfunction due to oxidative stress. Further, antioxidants, as well as alpha lipoic acid (ALA), may be a response to this pathological condition. The present study verified the action of ALA as a supplement in ration on glycemia and urinary vesicle structures of rats induced by streptozotocin. The rats were divided into 4 groups: Control (CG), Alpha Lipoic (ALAG), Diabetic control (DCG), and the Diabetic alpha lipoic (DALAG) group. For induction, the diabetic groups were initially induced with streptozotocin (dose 60 mg/kg). Subsequently, group glycemia was evaluated weekly. After 8 weeks, the rats were euthanized and the bladder was collected. The bladders were histologically processed and the slides were stained with Masson's Trichrome for the histomorphometry of epithelial height, connective and muscular tissue and coloration of PicroSirius Red for further analysis of collagen fibers of the bladder. The data of the glycemia demonstrated an inferior median in DALAG compared to DGC (p<0.01). The epithelial height and percentage of the muscle tissue were greater in DALAG compared to the DGC, but not significant. However, GDAL showed improvement in the organization of collagen fibers. In conclusion, bladder the morphology alterations caused by DM were not alleviated by the administration of ALA in 8 weeks of the experiments.

La diabetes mellitus (DM) es una afección marcada por hiperglucemia que causa complicaciones sistémicas, incluida la disfunción de la vejiga urinaria debido al estrés oxidativo. Además, los antioxidantes, así como el ácido alfa lipoico (ALA), pueden ser una respuesta a esta condición patológica. El presente estudio verificó la acción de ALA como suplemento en la ración sobre la glucemia y las estructuras de la vejiga urinaria de ratas inducidas por estreptozotocina. Las ratas se dividieron en 4 grupos: control (CG), alfa lipoico (ALAG), control diabético (DCG) y el grupo diabético alfa lipoico (DALAG). Para la inducción, los grupos diabéticos se aplicó estreptozotocina (dosis 60 mg/kg). Posteriormente, la glucemia grupal se evaluó semanalmente. Después de 8 semanas, las ratas se sacrificaron y se retiró la vejiga urinaria. Las vejigas se procesaron histológicamente y las muestras se tiñeron con tricromo de Masson para la histomorfometría y así evaluar la altura epitelial, el tejido conectivo y muscular. Además se tiñeron cond PicroSirius Red para un análisis posterior de las fibras colágenas de la vejiga urinaria. Los datos de la glucemia demostraron una mediana inferior en DALAG en comparación con DGC (p <0,01). La altura epitelial y el porcentaje de tejido muscular fueron mayores en DALAG en comparación con el DGC, pero no estadísticamente significativos. Sin embargo, GDAL mostró una mejora en la organización de las fibras de colágeno. En conclusión, la morfología de las alteraciones de la vejiga causada por DM no se alivió con la administración de ALA en 8 semanas de estudio.

Animals , Rats , Urinary Bladder/drug effects , Thioctic Acid/administration & dosage , Diabetes Mellitus, Experimental/drug therapy , Antioxidants/administration & dosage , Blood Glucose/analysis , Dietary Supplements