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1.
Int J Nanomedicine ; 15: 4877-4898, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753869

RESUMO

Background: Although dynamics and uses of modified nanoparticles (NPs) as orally administered macromolecular drugs have been researched for many years, measures of molecule stability and aspects related to important transport-related mechanisms which have been assessed in vivo remain as relatively under characterized. Thus, our aim was to develop a novel type of oral-based delivery system for insulin and to overcome barriers to studying the stability, transport mechanisms, and efficacy in vivo of the delivery system. Methods: NPs we developed and tested were composed of insulin (INS), dicyandiamide-modified chitosan (DCDA-CS), cell-penetrating octaarginine (r8), and hydrophilic hyaluronic acid (HA) and were physically constructed by electrostatic self-assembly techniques. Results: Compared to free-insulin, levels of HA-DCDA-CS-r8-INS NPs were retained at more desirable measures of biological activity in our study. Further, our assessments of the mechanisms for NPs suggested that there were high measures of cellular uptake that mainly achieved through active transport via lipid rafts and the macropinocytosis pathway. Furthermore, investigations of NPs indicated their involvement in caveolae-mediated transport and in the DCDA-CS-mediated paracellular pathway, which contributed to increasing the efficiency of sequential transportation from the apical to basolateral areas. Accordingly, high efficiency of absorption of NPs in situ for intestinal loop models was realized. Consequently, there was a strong induction of a hypoglycemic effect in diabetic rats of NPs via orally based administrations when compared with measures related to free insulin. Conclusion: Overall, the dynamics underlying and influenced by HA-DCDA-CS-r8-INS may hold great promise for stability of insulin and could help overcome interference by the epithelial barrier, and thus showing a great potential to improve the efficacy of orally related treatments.


Assuntos
Quitosana/química , Ácido Hialurônico/química , Insulina/administração & dosagem , Nanopartículas Multifuncionais/química , Nanopartículas/química , Administração Oral , Animais , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Morte Celular/efeitos dos fármacos , Quitosana/síntese química , Diabetes Mellitus Experimental/tratamento farmacológico , Impedância Elétrica , Endocitose/efeitos dos fármacos , Guanidinas/síntese química , Guanidinas/química , Humanos , Ácido Hialurônico/síntese química , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Muco/metabolismo , Nanopartículas/ultraestrutura , Ratos , Solubilidade , Suínos
2.
PLoS One ; 15(8): e0237660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841254

RESUMO

This study evaluated the influence of type 2 diabetes mellitus on bone loss, bone repair and cytokine production in hyperglycemic rats, treated or not with metformin. The animals were distributed as follow: Non-Hyperglycemic (NH), Non Hyperglycemic with Ligature (NH-L), Treated Non Hyperglycemic (TNH), Treated Non Hyperglycemic with Ligature Treated (TNH-L), Hyperglycemic (H), Treated Hyperglycemic (TH), Hyperglycemic with Ligature (H-L), Treated Hyperglycemic with Ligature (TH-L). At 40th day after induction of hyperglycemia, the groups NH-L, TNH-L, H-L, TH-L received a ligature to induce periodontitis. On the 69th, the TNH, TNH-L, TH, TH-L groups received metformin until the end of the study. Bone repair was evaluated at histometric and the expression levels of Sox9, RunX2 and Osterix. Analysis of the ex-vivo expression of TNF-α, IFN-γ, IL-12, IL-4, TGF-ß, IL-10, IL-6 and IL-17 were also evaluated. Metformin partially reverse induced bone loss in NH and H animals. Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis. The expression of SOX9 and RunX2 were also decreased by hyperglycemia and metformin treatment. Increased ex vivo levels of TNF-α, IL-6, IL-4, IL-10 and IL-17 was observed. Hyperglycemia promoted increased IL-10 levels compared to non-hyperglycemic ones. Treatment of NH with metformin was able to mediate increased levels of TNF-α, IL-10 and IL-17, whereas for H an increase of TNF-α and IL-17 was detected in the 24- or 48-hour after stimulation with LPS. Ligature was able to induce increased levels of TNF-α and IL-17 in both NH and H. This study revealed the negative impact of hyperglycemia and/or treatment with metformin in the bone repair via inhibition of transcription factors associated with osteoblastic differentiation.


Assuntos
Perda do Osso Alveolar/prevenção & controle , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Hiperglicemia/complicações , Metformina/administração & dosagem , Periodontite/prevenção & controle , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/metabolismo , Processo Alveolar/citologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/metabolismo , Processo Alveolar/patologia , Animais , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/genética , Diferenciação Celular/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Osteoblastos/fisiologia , Periodontite/etiologia , Periodontite/metabolismo , Ratos , Estreptozocina/toxicidade , Fatores de Transcrição/metabolismo
3.
Life Sci ; 258: 118155, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735887

RESUMO

AIMS: Aim of the present study was to investigate the effect of co-administration coenzyme Q10 and pioglitazone on the mRNA expression of adipocytokines in white adipose tissues of chemically induced type 2 diabetes mellitus in rats. MAIN METHODS: Diabetes was induced by administration of streptozotocin (65 mg/kg, i.p.), followed by nicotinamide (110 mg/kg, i.p.) 15 min later. The diabetic rats were treated coenzyme Q10 (Q10, 10 mg/kg, p.o.) or pioglitazone (PIO, 20 mg/kg, p.o.) alone and their combination for four weeks. Biochemical parameters like FBS level, insulin and HbA1c along with tissue levels of MDA, SOD, CAT and GSH were estimated. The mRNA levels of ADIPOQ, RBP4, RETN, IL-6 and TNF-α in White Adipose Tissue (WAT) were measured. KEY FINDINGS: Treatment with Q10 + PIO showed a significant reduction in the levels of FBS, HbA1c and a significant increase in insulin levels as compared to normal control group. Additionally, there was a significant change in the levels of biomarkers of oxidative stress after treatment with Q10 + PIO as compared to streptozotocin-nicotinamide group. Treatment with Q10 + PIO also significantly altered the mRNA expression of ADIPOQ, RETN, IL-6 and TNF-α when compared to monotherapy. However, mRNA expression of RBP4 did not alter in Q10 + PIO treated animal as compared to Q10 or PIO alone. SIGNIFICANCE: It is concluded that co-administration of Q10 and PIO has been shown the better therapeutic effect on the mRNA expression of adipocytokines and oxidative stress parameters as compared to either Q10 or PIO.


Assuntos
Adipocinas/genética , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Pioglitazona/uso terapêutico , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Sinergismo Farmacológico , Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Masculino , Pioglitazona/farmacologia , RNA Mensageiro/genética , Ratos , Ratos Wistar , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Vitaminas/farmacologia
4.
Int J Nanomedicine ; 15: 4191-4203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606672

RESUMO

Purpose: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. Material and Methods: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. Results: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. Conclusion: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.


Assuntos
Antrodia/química , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Reprodução , Ubiquinona/análogos & derivados , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Jejum/sangue , Glutationa Peroxidase/metabolismo , Humanos , Insulina/efeitos adversos , Insulina/sangue , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Estreptozocina , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
5.
Life Sci ; 257: 118120, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32693244

RESUMO

AIMS: Catalpol (Cat) can ameliorate oxide stress and inflammation caused by diabetic nephropathy (DN), but the molecular mechanisms are unclear. This study was designed to investigate the anti-diabetic effects of Cat and its potential mechanism. MAIN METHODS: We constructed high-fat diet/streptozotocin (HFD/STZ)-induced DN mice and high glucose (HG)-induced podocyte model. The hypoglycemic effect of Cat was analyzed by general features of DN mice. Kidney function was detected via ELISA assay and Western blotting. Renal histopathology analysis was conducted via hematoxylin and eosin (H&E), Masson and periodic acid-silver metheramine (PASM) staining. Cellular viability was measured by TUNEL assay. In order to further study the potential mechanisms of Cat, various proteins in AMPK/SIRT1/NF-κB pathway were detected in DN mice and podocytes with siRNA-AMPK intervention using Western blotting, respectively. KEY FINDINGS: We found hyperglycemia, renal structural and function abnormalities, and increased renal inflammation in DN mice. However, Cat effectively attenuated kidney damage caused by inflammation and increased AMPK, p-AMPK and SIRT1 levels. After AMPK-siRNA transfected into HG-induced podocyte model, AMPK, p-AMPK and SIRT1 levels were obviously decreased, while Cat reversed these chandes. The levels of p-NF-κB, ASC, Cleaved IL-1ß, NLRP3, Cleaved caspase1 and GSDMD-N significantly decreased by Cat treatment both in DN mice and podocyte model, which indicated that Cat could activate AMPK/SIRT1/NF-κB pathway. SIGNIFICANCE: Cat could effectively inhibit oxide stress and inflammation accompanied with pyroptosis and its mechanism might be related to AMPK/SIRT1/NF-κB pathway, indicating that Cat possessed potential value in the treatment of DN.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Glucosídeos Iridoides/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Western Blotting , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/patologia , Ensaio de Imunoadsorção Enzimática , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo
6.
PLoS One ; 15(7): e0228429, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722679

RESUMO

Diabetes mellitus (DM) causes ototoxicity by inducing oxidative stress, microangiopathy, and apoptosis in the cochlear sensory hair cells. The natural anti-oxidant pterostilbene (PTS) (trans-3,5-dimethoxy-4-hydroxystylbene) has been reported to relieve oxidative stress and apoptosis in DM, but its role in diabetic-induced ototoxicity is unclear. This study aimed to investigate the effects of dose-dependent PTS on the cochlear cells of streptozotocin (STZ)-induced diabetic rats. The study included 30 albino male Wistar rats that were randomized into five groups: non-diabetic control (Control), diabetic control (DM), and diabetic rats treated with intraperitoneal PTS at 10, 20, or 40 mg/kg/day during the four-week experimental period (DM + PTS10, DM + PTS20, and DM + PTS40). Distortion product otoacoustic emission (DPOAE) tests were performed at the beginning and end of the study. At the end of the experimental period, apoptosis in the rat cochlea was investigated using caspase-8, cytochrome-c, and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL). Quantitative real-time polymerase chain reaction was used to assess the mRNA expression levels of the following genes: CASP-3, BCL-associated X protein (BAX), and BCL-2. Body weight, blood glucose, serum insulin, and malondialdehyde (MDA) levels in the rat groups were evaluated. The mean DPOAE amplitude in the DM group was significantly lower than the means of the other groups (0.9-8 kHz; P < 0.001 for all). A dose-dependent increase of the mean DPOAE amplitudes was observed with PTS treatment (P < 0.05 for all). The Caspase-8 and Cytochrome-c protein expressions and the number of TUNEL-positive cells in the hair cells of the Corti organs of the DM rat group were significantly higher than those of the PTS treatment and control groups (DM > DM + PTS10 > DM + PTS20 > DM + PTS40 > Control; P < 0.05 for all). PTS treatment also reduced cell apoptosis in a dose-dependent manner by increasing the mRNA expression of the anti-apoptosis BCL2 gene and by decreasing the mRNA expressions of both the pro-apoptosis BAX gene and its effector CASP-3 and the ratio of BAX/BCL-2 in a dose-dependent manner (P < 0.05 compared to DM for all). PTS treatment significantly improved the metabolic parameters of the diabetic rats, such as body weight, blood glucose, serum insulin, and MDA levels, consistent with our other findings (P < 0.05 compared to DM for all). PTS decreased the cochlear damage caused by diabetes, as confirmed by DPOAE, biochemical, histopathological, immunohistochemical, and molecular findings. This study reports the first in vivo findings to suggest that PTS may be a protective therapeutic agent against diabetes-induced ototoxicity.


Assuntos
Cóclea/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Ototoxicidade/prevenção & controle , Estilbenos/farmacologia , Acústica , Animais , Peso Corporal/efeitos dos fármacos , Caspase 3/genética , Cóclea/patologia , Diabetes Mellitus Experimental/complicações , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Substâncias Protetoras/farmacologia , Ratos Wistar , Estilbenos/administração & dosagem , Estreptozocina , Proteína X Associada a bcl-2/genética
7.
Chem Biol Interact ; 330: 109167, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603660

RESUMO

Recently, it has been shown that drimane-type sesquiterpenoids isolated from Zygogynum pancheri, a species native to New Caledonia, possessed significant α-amylase inhibitory activities. To further explore their antidiabetic potential, we investigated the effect of 1ß-O-(E-cinnamoyl)-6α-hydroxy-9epi-polygodial (D) and 1ß-E-O-p-methoxycinnamoyl-bemadienolide (L), two of the most active compounds of the series, on diabetic model rats. Compounds D and L (2 mg kg/day) were daily and orally administrated for 30 days to streptozotocin (STZ) (150 mg/kg) induced male diabetic Wistar rats. Animals were allocated into five groups of six rats. Comparatively to diabetic rats, treatments with D and L compounds were able to significantly (P < 0.05) decrease Fasting Blood Glucose (FBG) (70.15%, 71.02%), serum total cholesterol (46.27% and 39.38%), triglycerides (56.60% and 58.15%), creatinine (37.31% and 36.49%) and uric acid levels (67.76% and 69.68%), respectively. Compounds D and L also restored the altered plasma enzyme (aspartate aminotransferase, AST (47.83% and 43.20%), alanine aminotransferase, ALT (49.76% and 48.35%, alkaline phosphatase, ALP (72.78% and 73.21%)) and lactate dehydrogenase, LDH (47.95% and 53.93%) levels to near normal, respectively. Administration of Glymepiride, significantly (p < 0.05) reduced FBG (73.94%) in STZ induced diabetic rats. Additionally, the compounds D and L exhibited inhibitory effects in vivo on lipase activity of diabetic rats (54.83% and 52.25%), respectively. The outcomes of this study suggested that these two drimanes could be considered as efficient hypoglycemic, hypolipidemic and antiobesity agents for diabetes management and its complications.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Sesquiterpenos Policíclicos/isolamento & purificação , Animais , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/farmacologia , Masculino , Nova Caledônia , Extratos Vegetais/química , Sesquiterpenos Policíclicos/farmacologia , Ratos , Ratos Wistar , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Winteraceae/química
8.
Arterioscler Thromb Vasc Biol ; 40(9): 2084-2094, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673528

RESUMO

OBJECTIVE: Increased postprandial lipemia (PPL) is an independent risk factor for atherosclerotic cardiovascular diseases. PCSK9 (Proprotein convertase subtilisin kexin type 9) is an endogenous inhibitor of the LDLR (low-density lipoprotein receptor) pathway. We previously showed that PCSK9 inhibition in mice reduces PPL. However, the relative contribution of intracellular intestinal PCSK9 or liver-derived circulating PCSK9 to this effect is still unclear. Approach and Results: To address this issue, we generated the first intestine-specific Pcsk9-deficient (i-Pcsk9-/-) mouse model. PPL was measured in i-Pcsk9-/- as well as in wild-type and streptozotocin-induced diabetic mice following treatment with a PCSK9 monoclonal antibody (alirocumab). Blocking the circulating form of PCSK9 with alirocumab significantly reduced PPL, while overexpressing human PCSK9 in the liver of full Pcsk9-/- mice had the opposite effect. Alirocumab regulated PPL in a LDLR-dependent manner as this effect was abolished in Ldlr-/- mice. In contrast, i-Pcsk9-/- mice did not exhibit alterations in plasma lipid parameters nor in PPL. Finally, PPL was highly exacerbated by streptozotocin-induced diabetes mellitus in Pcsk9+/+ but not in Pcsk9-/- mice, an effect that was mimicked by the use of alirocumab in streptozotocin-treated Pcsk9+/+ mice. CONCLUSIONS: Taken together, our data demonstrate that PPL is significantly altered by full but not intestinal PCSK9 deficiency. Treatment with a PCSK9 monoclonal antibody mimics the effect of PCSK9 deficiency on PPL suggesting that circulating PCSK9 rather than intestinal PCSK9 is a critical regulator of PPL. These data validate the clinical relevance of PCSK9 inhibitors to reduce PPL, especially in patients with type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Hiperlipidemias/sangue , Intestinos/enzimologia , Lipídeos/sangue , Pró-Proteína Convertase 9/sangue , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/enzimologia , Hiperlipidemias/enzimologia , Hiperlipidemias/genética , Hiperlipidemias/prevenção & controle , Hipolipemiantes/farmacologia , Intestinos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Período Pós-Prandial , Pró-Proteína Convertase 9/antagonistas & inibidores , Pró-Proteína Convertase 9/deficiência , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Receptores de LDL/metabolismo
9.
Life Sci ; 258: 118146, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32721462

RESUMO

OBJECTIVE: To investigate protective efficacies and mechanisms of dencichine on diabetic kidney injury via in vitro and in vivo assays. METHODS: Effects of dencichine on hydrogen peroxide (H2O2) induced oxidative damage in HK-2 renal cells were assessed by CCK-8 method. Forty streptozotocin (STZ)-induced diabetic rats with kidney injury were randomly divided into negative control group, three doses of dencichine (40, 80 and 160 mg/kg) groups. Blood biochemical and kidney related indexes as well adrenal morphological changes, apoptosis and autophagy related markers of diabetic rats were measured. RESULTS: Cell viability of HK-2 cells with oxidative damage induced by H2O2 was significantly improved by dencichine with 160 µg/mL for 43.7% and 320 µg/mL for 52.9% compared with control. Moreover, the decreased reactive oxygen species (ROS), and increased intracellular antioxidant enzymes including GPX1, SOD2 and GSH were showed in dencichine groups. In addition, incubation of dencichine in HK-2 cells promoted the increase of p-AMPK, BCL2, LC3, decreased activation of p-mTOR, BAX and Caspase 3. Chronic treatment of dencichine improved the STZ-induced diabetic characteristics of model rats. Further histopathological examination of renal tissues revealed 12-week treatment of dencichine effectively improved the morphology of nephropathy in diabetic rats. Moreover, dencichine also ameliorated excessive oxidation stress, down-regulated renal cell apoptosis and fibrosis related proteins, thereby protected renal tissues in diabetic rats. CONCLUSION: Dencichine ameliorated STZ-induced kidney injury mainly through inhibiting oxidative stress, reducing renal fibrosis, increasing autophagy, and reducing the renal cell apoptosis related proteins to protect nephrocytes and decrease renal tissue damage.


Assuntos
Diamino Aminoácidos/uso terapêutico , Antioxidantes/uso terapêutico , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Fibrose , Humanos , Rim/metabolismo , Rim/patologia , Masculino , Ratos , Ratos Sprague-Dawley
10.
Environ Sci Pollut Res Int ; 27(32): 40525-40536, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32666453

RESUMO

Diabetes mellitus (DM) is one of the most dangerous incurable diseases that affects a large number of people worldwide. Artemisia species have various protective activities and are widely used for the control of diabetes in folkloric medicine. Therefore, the current study was designed to illustrate the protective effect of oral administration of Artemisia judaica extract (AjE) against hepatorenal damage in a high-fat diet/streptozotocin (HFD/STZ) rat model of hyperlipidemia and hyperglycemia. Animals were divided into five groups-control, AjE, HFD/STZ, HFD/STZ-AjE (300 mg/kg), and HFD/STZ-MET (100 mg/kg)-and treated daily for 28 days. The results revealed that STZ-injected rats showed marked hyperglycemia and hypoinsulinemia in addition to high levels of cholesterol, triglycerides, and low- and high-density lipoproteins compared to control rats. Significant elevations in hepatic (AST and ALT) and renal (urea, uric acid, and creatinine) function markers were observed in the serum of diabetic rats. Additionally, STZ injection caused remarkable elevations in lipid peroxidation and nitric oxide levels as well as suppression of antioxidant markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione). Marked elevations in TNF-α and Bax levels with a decline in Bcl-2 levels were detected after STZ injection. Furthermore, TGF-ß1 expression levels were significantly upregulated in the liver and kidney tissues. Rats that received AjE or MET showed significant improvement in most of the aforementioned parameters, and the protective efficacy was higher for AjE than for MET. Histopathological screening confirmed the biochemical findings. Conclusively, our results illustrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and antiapoptotic activities of AjE against hepatorenal injury in HFD/STZ-induced diabetes.


Assuntos
Artemisia , Diabetes Mellitus Experimental , Metformina , Animais , Antioxidantes , Glicemia , Diabetes Mellitus Experimental/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Fígado , Estresse Oxidativo , Extratos Vegetais/farmacologia , Ratos , Estreptozocina
11.
J Pharmacol Sci ; 143(4): 307-314, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32536591

RESUMO

Rutaecarpine, an indolopyridoquinazoline alkaloid, attracted attentions because of possessing various biological activities. The objective of this study was to investigate the effect of rutaecarpine on glucose and lipid metabolism in high fat diet-multiple low dose streptozotocin induced type 2 diabetic (HFD-db) mice and to understand the mechanism of action. HFD-db mice showed impaired glucose metabolism and lipid profile. Oral administration of rutaecarpine reduced the blood glucose levels, decreased blood hemoglobin A1c (HbA1c) levels, improved glucose tolerance and restored insulin sensitivity in HFD-db mice. Rutaecarpine also decreased body weight gain, water intake and visceral fat gain in HFD-db mice. Total cholesterol, triglycerides, very low density lipoprotein and low density lipoprotein were reduced and high density lipoprotein level was augmented in rutaecarpine treated HFD-db mice. Rutaecarpine also reduced the elevated levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, urea and creatinine in HFD-db mice. Rutaecarpine significantly promoted the rate of glucose consumption, glucose uptake and glycolysis in C2C12 myotubes. Western blotting results showed that rutaecarpine augmented p-GSK-3ß and p-AMPK expression, and suppressed G6Pase expression in HepG2 cells. These results suggest that rutaecarpine might be having therapeutic importance to fight against type 2 diabetes mellitus associated with dyslipidemia.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Hipoglicemiantes , Alcaloides Indólicos/farmacologia , Fígado/metabolismo , Quinazolinas/farmacologia , Animais , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Tipo 2/etiologia , Modelos Animais de Doenças , Alcaloides Indólicos/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , Quinazolinas/uso terapêutico
12.
PLoS One ; 15(6): e0235221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584888

RESUMO

Ficus krishnae stem bark and leaves are used for diabetes treatment in traditional medicines. Stem bark of F. krishnae was sequentially extracted with hexane, methanol and water, and these extracts were tested for their antihyperglyceamic activity by oral glucose tolerance test (OGTT) in overnight fasted glucose loaded normal rats. Hexane extract showed significant glucose lowering activity in OGTT, and the triterpene alcohols (cycloartenol+24-methylenecycloartanol) (CA+24-MCA) were isolated together from it by activity guided isolation and characterized by NMR and mass spectroscopy. The ratio of the chemical constituents CA and 24-MCA in (CA+24-MCA) was determined as 2.27:1.00 by chemical derivatization and gas chromatographic quantification. (CA+24-MCA) in high fat diet-streptozotocin induced type II diabetic rats showed significant antidiabetes activity at 1 mg/kg and ameliorated derailed blood glucose and other serum biochemical parameters. Cytoprotective activity of (CA+24-MCA) from glucose toxicity was evaluated in cultured RIN-5F cells by MTT assay and fluorescent microscopy. (CA+24-MCA) in in vitro studies showed enhanced cell viability in RIN-5F cells and significant protection of beta cells from glucose toxicity. Both in in vivo and in vitro studies (CA+24-MCA) showed enhancement in insulin release from the beta cells. In short term toxicity studies in mice (CA+24-MCA) did not show any conspicuous toxic symptoms. The combination of the phytosterols (CA+24-MCA) obtained through activity guided isolation of the stem bark of F. krishnae showed significant activity, and therefore is a promising candidate for new generation antidiabetes drug development.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ficus/química , Hipoglicemiantes/uso terapêutico , Fitosteróis/química , Triterpenos/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Ficus/metabolismo , Teste de Tolerância a Glucose , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Conformação Molecular , Fitosteróis/isolamento & purificação , Fitosteróis/uso terapêutico , Caules de Planta/química , Caules de Planta/metabolismo , Ratos , Ratos Wistar , Triterpenos/isolamento & purificação , Triterpenos/uso terapêutico
13.
Int. j. morphol ; 38(3): 627-633, June 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098298

RESUMO

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.


Assuntos
Animais , Ratos , Bexiga Urinária/efeitos dos fármacos , Ácido Tióctico/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Antioxidantes/administração & dosagem , Glicemia/análise , Suplementos Nutricionais
14.
J Environ Pathol Toxicol Oncol ; 39(1): 89-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479015

RESUMO

Oxidative stress and inflammation are regarded as prime reasons for the progression and development of diabetic retinopathy. Currently, nuclear factor erythroid-2-related factor 2 (Nrf2), thioredoxin interacting protein (TXNIP) and NLRP3 inflammasome pathways are under increasing focus in research on oxidative stress and inflammation-related diseases. On the other hand, tilianin (TN) has received much attention because of its various pharmacological properties. Based on results of these studies, this investigation was performed to inspect the therapeutic efficiency of TN on the retina in diabetic rats. Rats were arbitrarily assigned to three groups: control group, diabetic group, and diabetic plus TN (20 mg/ kg body weight for 42 days, orally) group. TN supplementation in diabetic rats, their food intake, fasting blood glucose status, glycosylated hemoglobin (HbA1c) levels were drastically reduced, and there was a marked augmentation in serum insulin status. TN treatment of diabetic rats increased mRNA expression of Nrf2 and its target gene, HO-1, and noticeably decreased the malondialdehyde status. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX) were increased relative to diabetic rats. Furthermore, administering TN to the diabetic rats resulted in decreased expression of TXNIP, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1ß proteins and decreased distribution of TXNIP, NLRP3, ASC, and caspase-1 proteins in retinas. In addition, TN treatment ameliorated morphological and morphometric changes in the retinas of diabetic rats. Together, all of these findings provide clear evidence that TN treatment of diabetic rats attenuated diabetic retinal changes through its hypoglycemic, antioxidant, and anti-inflammatory properties. The antioxidant and anti-inflammatory effects in diabetic retinas occur at least in part through the modulation of Nrf2/TXNIP/NLRP3 inflammasome pathways, which may have remedial benefits in the healing of diabetic retinopathy.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/farmacologia , Glicosídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais/análise , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Retina/patologia
15.
Braz J Med Biol Res ; 53(7): e9628, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520209

RESUMO

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-ß1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inflamação/prevenção & controle , Ophiopogon/química , Estresse Oxidativo/efeitos dos fármacos , Saponinas/uso terapêutico , Espirostanos/uso terapêutico , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina
17.
Life Sci ; 256: 117887, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497629

RESUMO

Vascular complications are a leading cause of morbidity and mortality among diabetic patients. This work aimed to investigate possible influences of dimethyl fumarate (DMF) on streptozotocin (STZ) diabetes-associated vascular complications in rats, exploring its potential to modulate ROS-TXNIP-NLRP3 inflammasome pathway. Two weeks after induction of diabetes (via a single injection of 50 mg/kg STZ, i.p.), diabetic rats were administered either DMF (25 mg/kg/day) or its vehicle for further eight weeks. Age-matched normal and DMF-administered non-diabetic rats served as controls. DMF treatment elicited a mild ameliorative effect on diabetic glycemia. DMF reduced serum TG and AGE levels and enhanced serum HDL-C concentrations in diabetic rats. Moreover, DMF significantly diminished aortic levels of ROS and MDA and restored aortic GSH, SOD and Nrf2 to near-normal levels in STZ rats. Aortic mRNA levels of TXNIP, NLRP3 and NF-κB p65 in diabetic rats were significantly reduced by DMF treatment. Serum and aortic protein levels of TXNIP and aortic contents of IL-1ß, iNOS, NLRP3 and TGF-ß1 were significantly lower in DMF-diabetic animals than non-treated diabetic rats. Furthermore, protein expression of TNF-α and caspase-3 in diabetic aortas was greatly attenuated by DMF administration. DMF enhanced eNOS mRNA and protein levels and increased bioavailable NO in diabetic aortas. Functionally, DMF attenuated contractile responses of diabetic aortic rings to KCl and phenylephrine and enhanced their relaxant responses to acetylcholine. DMF also mitigated diabetes-induced fibrous tissue proliferation in aortic tunica media. Collectively, these findings demonstrate that DMF offered vasculoprotective influences on diabetic aortas via attenuation of ROS-TXNIP-NLRP3 inflammasome pathway.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/metabolismo , Fumarato de Dimetilo/uso terapêutico , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Biomarcadores/metabolismo , Caspase 3/metabolismo , Proteínas de Ciclo Celular/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Angiopatias Diabéticas/sangue , Fumarato de Dimetilo/farmacologia , Interleucina-1beta/metabolismo , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Oxirredução , Ratos Sprague-Dawley , Estreptozocina , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Life Sci ; 253: 117727, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32371063

RESUMO

AIMS: To unravel the underlying mechanism of hepatic inflammation during type 2 diabetes (T2DM), we established the diabetic rat model by feeding with high fructose diet for twenty weeks and studied the involvement of inflammasome in the liver of these rats. MATERIALS AND METHODS: Male SD rats weighing 180-200 g were divided in four groups: 1) Control (Con group) rats were fed with corn starch diet, 2) diabetic (Dia group) rats were fed with 65% of fructose, 3) diabetic along with resveratrol (10 mg/kg/day); p.o. (Dia + Resv group) and 4) diabetic along with metformin (300 mg/kg/day); p.o. (Dia + Met group), for twenty weeks. We evaluated the establishment of T2DM in fructose fed rats and the effect of resveratrol and metformin treatment on different diabetic parameters in these rats. Further we investigated the role of NLRP3 inflammasome on T2DM induced liver inflammation and effect of resveratrol and metformin treatment on NLRP3 inflammasome driven inflammatory response. KEY FINDINGS: Rats from Dia group; manifested insulin resistance, hyperinsulinemia, hyperglycemia, elevated uric acid along with hypertriglyceridemia after fructose feeding for twenty weeks. Mostly, above parameters were attenuated in resveratrol and metformin treated groups. Expression of NLRP3 inflammasome components in liver were increased in Dia group rats with elevated transcript levels of pro-inflammatory cytokines. Histopathological examination revealed increase in glycogen content and fibrosis in Dia group rats; which was considerably reduced with resveratrol and metformin treatment. SIGNIFICANCE: Our study suggests that management of inflammation may be considered as an alternative approach to prevent liver tissue injury during chronic diabetic condition.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inflamação/prevenção & controle , Metformina/farmacologia , Resveratrol/farmacologia , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Frutose/administração & dosagem , Hipoglicemiantes/farmacologia , Inflamassomos/metabolismo , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-Dawley
19.
Life Sci ; 256: 117855, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32473245

RESUMO

OBJECTIVE: Subjects with type 2 diabetes (T2D) have lower circulating hydrogen sulfide (H2S) levels following myocardial ischemia and a higher risk of mortality. The aim of this study was to determine the dose-dependent favorable effects of sodium hydrosulfide (NaSH) on myocardial ischemia-reperfusion (IR) injury in rats with T2D. METHODS: T2D was induced using a high-fat diet (HFD) and low-dose of streptozotocin. Rats were divided into control, T2D, and T2D + NaSH groups. NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg) was administered intraperitoneally for 9 weeks. At the end of the study, heart from all rats were isolated and left ventricular developed pressure (LVDP) and the peak rates of positive and negative changes in LV pressure (±dp/dt) were recorded during baseline and following myocardial IR injury. In addition, infarct size as well as mRNA expression of H2S- and nitric oxide (NO)-producing enzymes were measured. RESULTS: In diabetic rats, NaSH only at doses of 0.56 and 1.6 mg/kg increased recovery of LVDP (16% and 42%), +dp/dt (25% and 35%) and -dp/dt (23% and 32%) as well as decreased infarct size (44% and 35%). At these doses, NaSH increased expressions of cystathionine γ-lyase (CSE) (440% and 271%) and endothelial NO synthase (eNOS) (232% and 148%) but it decreased the expressions of inducible NOS (iNOS) (55% and 71%). NaSH at 0.28, 2.8 and 5.6 mg/kg had no significant effects on these parameters. CONCLUSION: NaSH had a bell-shaped cardioprotective effect against myocardial IR injury in rats with T2D. Higher tolerance to IR injury in heart isolated from type 2 diabetic rats treated with intermediate doses of NaSH is associated with higher CSE-derived H2S and eNOS-derived NO as well as lower iNOS-derived NO.


Assuntos
Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Sulfetos/farmacologia , Animais , Cardiotônicos/administração & dosagem , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica , Relação Dose-Resposta a Droga , Sulfeto de Hidrogênio/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/complicações , Ratos , Ratos Wistar , Estreptozocina , Sulfetos/administração & dosagem
20.
Life Sci ; 254: 117777, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407839

RESUMO

AIM: Inflammatory cascade and oxidative stress play a central role in diabetic peripheral neuropathy via activation of inflammatory cytokines. Escin has potent antioxidant and anti-inflammatory properties. Hence, the present study was conducted to evaluate the effect of escin on diabetic peripheral neuropathy in streptozotocin (STZ) induced diabetes in rats. MAIN METHODS: Diabetes was induced in rats with streptozotocin (55 mg/kg). The animals with blood glucose above 250 mg/dl were randomized in different groups. Animals were treated with escin at a dose of 5, 10 and 20 mg/kg after six weeks of diabetes induction for the next four weeks. After completion of treatment, various parameters like glucose, thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia and nerve conduction velocities were evaluated. Oxidative stress parameters like malondialdehyde, catalase, reduced glutathione and superoxide dismutase were performed in sciatic nerves. Histopathology study of sciatic nerves was also studied. KEY FINDINGS: Escin treatment significantly reduced plasma glucose, thermal hyperalgesia, mechanical hyperalgesia and mechanical allodynia as compared to diabetic animals. The motor nerve conduction velocity and sensory nerve conduction velocities were significantly improved in diabetic animals treated with escin. Escin significantly normalized oxidative stress parameters. Escin treatment also prevented progression of neuronal damage by reducing demyelination, leukocytic infiltration in sciatic nerves as compared to diabetic animals. SIGNIFICANCE: From the results of study it can be concluded that escin can be a useful option for management of diabetic peripheral neuropathy.


Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Escina/farmacologia , Animais , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Escina/metabolismo , Hiperalgesia/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Estreptozocina/farmacologia , Superóxido Dismutase/metabolismo
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