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1.
Wei Sheng Yan Jiu ; 49(5): 785-822, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33070825

RESUMO

OBJECTIVE: Establish the prokaryotic expression system of Amuc_1100 protein from Akkermansia muciniphila, and analyze the effects of this protein on the body weight, blood glucose, intestinal barrier function and Akkermansia muciniphila abundance in rats fed with high-fat diet combined streptozotocin(STZ)injection. METHODS: PCR product of Amuc_1100 Gene(Gene ID: 34174504) was linked to the double enzyme-digested pET-26 b plasmid vector. The recombinant expression plasmid pET-26 b-Amuc_1100 then transformed into E. Coli BL21. The verified clones through sequence analysis were induced by the addition of IPTG. High-fat diet rats were interfered with the purified protein at high and low doses. The changes of body weight, blood glucose, intestinal barrier function and Akkermansia muciniphila abundance were analyzed. RESULTS: The recombinant expression plasmid pET-26 b-Amuc_1100 was successfully constructed. The sequencing result showed 100% similarity to the Amuc_1100 gene in GenBank. The molecular weight of the protein obtained was 42 kDa. The intervention of Amuc_1100 protein can reduce the weight of rats fed with high-fat diet combined STZ injection to some extent, improve barrier function and increase the abundance of Akkermansia muciniphila in intestine. CONCLUSION: The prokaryotic expression system of Amuc_1100 protein was successfully constructed, which has a certain regulatory effect on rats fed with high-fat diet combined STZ injection.


Assuntos
Dieta Hiperlipídica , Escherichia coli , Animais , Dieta Hiperlipídica/efeitos adversos , Escherichia coli/genética , Ratos , Estreptozocina/toxicidade , Verrucomicrobia
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.
An Acad Bras Cienc ; 92(2): e20191340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813865

RESUMO

Type 2 diabetes mellitus (T2DM) is associated with an increase of premature appearance of several disorders such as cardiac complications. Thus, we test the hypothesis that a combination of a high fat diet (HFD) and low doses of streptozotocin (STZ) recapitulate a suitable mice model of T2DM to study the cardiac mitochondrial disturbances induced by this disease. Animals were divided in 2 groups: the T2DM group was given a HFD and injected with 2 low doses of STZ, while the CNTRL group was given a standard chow and a buffer solution. The combination of HFD and STZ recapitulate the T2DM metabolic profile showing higher blood glucose levels in T2DM mice when compared to CNTRL, and also, insulin resistance. The kidney structure/function was preserved. Regarding cardiac mitochondrial function, in all phosphorylative states, the cardiac mitochondria from T2DM mice presented reduced oxygen fluxes when compared to CNTRL mice. Also, mitochondria from T2DM mice showed decreased citrate synthase activity and lower protein content of mitochondrial complexes. Our results show that in this non-obese T2DM model, which recapitulates the classical metabolic alterations, mitochondrial function is impaired and provides a useful model to deepen study the mechanisms underlying these alterations.


Assuntos
Diabetes Mellitus Tipo 2 , Animais , Glicemia , Resistência à Insulina , Camundongos , Mitocôndrias , Estreptozocina
4.
PLoS One ; 15(8): e0237669, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810137

RESUMO

Pancreatic beta cell death is a hallmark of type 1 and 2 diabetes (T1D/T2D), but the underlying molecular mechanisms are incompletely understood. Key proteins of the DNA damage response (DDR), including tumor protein P53 (P53, also known as TP53 or TRP53 in rodents) and Ataxia Telangiectasia Mutated (ATM), a kinase known to act upstream of P53, have been associated with T2D. Here we test and compare the effect of ATM and P53 ablation on beta cell survival in the rat beta cell line Ins1E. We demonstrate that ATM and P53 differentially regulate beta cell apoptosis induced upon fundamentally different types of diabetogenic beta cell stress, including DNA damage, inflammation, lipotoxicity and endoplasmic reticulum (ER) stress. DNA damage induced apoptosis by treatment with the commonly used diabetogenic agent streptozotocin (STZ) is regulated by both ATM and P53. We show that ATM is a key STZ induced activator of P53 and that amelioration of STZ induced cell death by inhibition of ATM mainly depends on P53. While both P53 and ATM control lipotoxic beta cell apoptosis, ATM but not P53 fails to alter inflammatory beta cell death. In contrast, tunicamycin induced (ER stress associated) apoptosis is further increased by ATM knockdown or inhibition, but not by P53 knockdown. Our results reveal differential roles for P53 and ATM in beta cell survival in vitro in the context of four key pathophysiological types of diabetogenic beta cell stress, and indicate that ATM can use P53 independent signaling pathways to modify beta cell survival, dependent on the cellular insult.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Sobrevivência Celular/genética , Células Secretoras de Insulina/patologia , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Diabetes Mellitus/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Técnicas de Silenciamento de Genes , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Ratos , Estreptozocina/toxicidade , Tunicamicina/toxicidade
5.
PLoS One ; 15(8): e0237305, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822421

RESUMO

Diabetes can elicit direct deleterious effects on the myocardium, independent of coronary artery disease or hypertension. These cardiac disturbances are termed diabetic cardiomyopathy showing increased risk of heart failure with or without reduced ejection fraction. Presently, there is no specific treatment for this type of cardiomyopathy and in the case of type I diabetes, it may start in early childhood independent of glycemic control. We hypothesized that alterations in isolated myocyte contractility and cardiac function are present in the early stages of experimental diabetes in rats before overt changes in myocardium structure occur. Diabetes was induced by single-dose injection of streptozotocin (STZ) in rats with data collected from control and diabetic animals 3 weeks after injection. Left ventricle myocyte contractility was measured by single-cell length variation under electrical stimulation. Cardiac function and morphology were studied by high-resolution echocardiography with pulsed-wave tissue Doppler imaging (TDI) measurements and three-lead surface electrocardiogram. Triglycerides, cholesterol and liver enzyme levels were measured from plasma samples obtained from both groups. Myocardial collagen content and perivascular fibrosis of atria and ventricle were studied by histological analysis after picrosirius red staining. Diabetes resulted in altered contractility of isolated cardiac myocytes with increased contraction and relaxation time intervals. Echocardiography showed left atrium dilation, increased end-diastolic LV and posterior wall thickness, with reduced longitudinal systolic peak velocity (S') of the septum mitral annulus at the apical four-chamber view obtained by TDI. Triglycerides, aspartate aminotransferase and alkaline phosphatase were elevated in diabetic animals. Intertitial collagen content was higher in atria of both groups and did not differ among control and diabetic animals. Perivascular intramyocardial arterioles collagen did not differ between groups. These results suggest that alterations in cardiac function are present in the early phase in this model of diabetes type 1 and occur before overt changes in myocardium structure appear as evaluated by intersticial collagen deposition and perivascular fibrosis of intramyocardial arterioles.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Cardiomiopatias Diabéticas/fisiopatologia , Contração Miocárdica , Miócitos Cardíacos/patologia , Animais , Células Cultivadas , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/patologia , Cardiomiopatias Diabéticas/induzido quimicamente , Cardiomiopatias Diabéticas/patologia , Ratos , Estreptozocina
6.
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
7.
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
8.
Chem Biol Interact ; 328: 109197, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32710900

RESUMO

The present study was undertaken to assess the effect of imatinib mesylate; a tyrosine kinase inhibitor and a well-known anticancer with numerous medical benefits on blood sugar levels, insulin, and glucagon secretion in an experimental model of STZ-induced diabetes mellitus. Type 1 diabetes mellitus (T1DM) was induced by a single I.P. injection of Streptozotocin (STZ) (50 mg/kg) in male Sprague-Dawley rats. Daily oral imatinib (10 mg/kg) and (20 mg/kg) for 4 weeks induced a significant attenuation in signs of DM in rats reflected in their assessed lab values. Biomarkers of cell injury, tissue necrosis, and apoptosis; caspase-3 were significantly reduced with imatinib treatment. Furthermore, pancreatic antioxidants defenses of which; superoxide dismutase (SOD) and catalase activities, reduced glutathione (GSH) concentration, and total antioxidant capacity have significantly improved with a simultaneous reduction in malondialdehyde (MDA) content. Histopathologically, imatinib treatment was associated with a minimal pancreatic injury and marked restoration of insulin content in ß-cells. Moreover, imatinib treatment revealed a significant reduction in the infiltration of macrophages in ß-cells. Imatinib's ameliorative impact on DM may be attributed to it's mediated protection and preservation of pancreatic ß-cells function and the improvement in serum insulin levels and hence the improvement of blood glucose and overall glycemic control.


Assuntos
Diabetes Mellitus Experimental/patologia , Mesilato de Imatinib/farmacologia , Células Secretoras de Insulina/metabolismo , Administração Oral , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antioxidantes/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Catalase/metabolismo , Diabetes Mellitus Experimental/sangue , Modelos Animais de Doenças , Glucagon/sangue , Glutationa/metabolismo , Insulina/sangue , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Estreptozocina , Superóxido Dismutase/metabolismo
9.
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
10.
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
11.
Life Sci ; 257: 117918, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32525002

RESUMO

OBJECTIVE: To investigate protective efficacies and mechanisms of Cathelicidin-BF (BF-30) peptide on streptozotocin (STZ)-induced diabetic kidney injury. METHODS: Effects of BF-30 on hydrogen peroxide induced oxidative damage in HK-2 renal cells were assessed by CCK-8 method. Forty STZ-induced diabetic rats with kidney injury were randomly divided into model control group, BF-30 group at different doses (0.1, 0.3 and 0.9 mg/kg). Blood biochemical and kidney related indexes as well adrenal morphological changes, inflammation related markers of diabetic rats were measured. RESULTS: Cell viability of HK-2 cells with oxidative damage induced by hydrogen peroxide were significantly improved by BF-30 with 0.8 µg/mL for 56.5% and 1.6 µg/mL for 82.3% compared with control. Moreover, the decreased reactive oxygen species (ROS), and increased intracellular antioxidant enzymes GPX1, SOD2 and GSH were showed in BF-30 treated groups. In addition, co-incubation of BF-30 in HK-2 cells promoted the increase of p-AMPK and LC3, decreased activation of p-mTOR, BAX and Caspase 3. Chronic treatment of BF-30 improved the STZ-induced diabetic characteristics of diabetic kidney disease (DKD) model rats. Further renal histopathological examination revealed 12-week treatment of BF-30 effectively improved the morphology of nephropathy in DKD rats. Moreover, BF-30 also could ameliorate excessive oxidative stress, renal cell apoptosis and fibrosis, thereby protects renal tissues. CONCLUSION: BF-30 exerted protective effects on STZ-induced kidney injury mainly through the inhibiting oxidative stress in kidney tissue, reducing renal fibrosis, increasing autophagy, and reducing the renal cell apoptosis related proteins to decrease the cell damage and protect nephrocytes.


Assuntos
Lesão Renal Aguda/prevenção & controle , Catelicidinas/farmacologia , Rim/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Catelicidinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Feminino , Fibrose/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Rim/patologia , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina/farmacologia
12.
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
13.
Anat Sci Int ; 95(4): 523-539, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32476103

RESUMO

Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease caused by the destruction of pancreatic ß-cells. Human dental pulp stem cells represent a promising source for cell-based therapies, owing to their easy, minimally invasive surgical access, and high proliferative capacity. It was reported that human dental pulp stem cells can differentiate into a pancreatic cell lineage in vitro; however, few studies have investigated their effects on diabetes. Our study aimed to investigate the therapeutic potential of intravenous and intrapancreatic transplantation of human dental pulp stem cells in a rat model of streptozotocin-induced type 1 diabetes. Forty Sprague Dawley male rats were randomly categorized into four groups: control, diabetic (STZ), intravenous treatment group (IV), and intrapancreatic treatment group (IP). Human dental pulp stem cells (1 × 106 cells) or vehicle were injected into the pancreas or tail vein 7 days after streptozotocin injection. Fasting blood glucose levels were monitored weekly. Glucose tolerance test, rat and human serum insulin and C-peptide, pancreas histology, and caspase-3, vascular endothelial growth factor, and Ki67 expression in pancreatic tissues were assessed 28 days post-transplantation. We found that both IV and IP transplantation of human dental pulp stem cells reduced blood glucose and increased levels of rat and human serum insulin and C-peptide. The cells engrafted and survived in the streptozotocin-injured pancreas. Islet-like clusters and scattered human dental pulp stem cells expressing insulin were observed in the pancreas of diabetic rats with some difference in the distribution pattern between the two injection routes. RT-PCR analyses revealed the expression of the human-specific pancreatic ß-cell genes neurogenin 3 (NGN3), paired box 4 (PAX4), glucose transporter 2 (GLUT2), and insulin in the pancreatic tissues of both the IP and IV groups. In addition, the transplanted cells downregulated the expression of caspase-3 and upregulated the expression of vascular endothelial growth factor and Ki67, suggesting that the injected cells exerted pro-angiogenetic and antiapoptotic effects, and promoted endogenous ß-cell replication. Our study is the first to show that human dental pulp stem cells can migrate and survive within streptozotocin-injured pancreas, and induce antidiabetic effects through the differentiation and replacement of lost ß-cells and paracrine-mediated pancreatic regeneration. Thus, human dental pulp stem cells may have therapeutic potential to treat patients with long term T1DM.


Assuntos
Polpa Dentária/citologia , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Pâncreas/fisiologia , Transplante de Células-Tronco , Células-Tronco/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Caspase 3/metabolismo , Diferenciação Celular , Movimento Celular , Sobrevivência Celular , Modelos Animais de Doenças , Transportador de Glucose Tipo 2/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Masculino , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição Box Pareados/metabolismo , Pâncreas/citologia , Pâncreas/metabolismo , Ratos , Ratos Sprague-Dawley , Regeneração , Estreptozocina
14.
Vascul Pharmacol ; 131: 106761, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32585189

RESUMO

AIMS: Diabetes-induced retinal vascular cell death aggravates diabetic retinopathy (DR) to the proliferative stage and blindness. Pericytes play a crucial role in retinal capillaries survival, stability, and angiogenesis. Ephrin-B2 is a tyrosine kinase that regulates pericytes/endothelial cells communication during angiogenesis; yet, its role in DR is still unclear. We hypothesize that diabetes increases Ephrin-B2 signaling in pericytes, which contributes to inflammation and retinal vascular cell death. METHODS: Selective inhibition of the Ephrin-B2 expression in the retinal pericytes was achieved using an intraocular injection of adeno-associated virus (AAV) with a specific pericyte promotor. Vascular death was determined by retinal trypsin digest. Pathological angiogenesis was assessed using the oxygen-induced retinopathy model in pericyte-Ephrin-B2 knockout mice, wild type, and wild type injected with AAV. Angiogenic properties, inflammatory, and apoptotic markers were measured in human retinal pericytes (HRP) grown under diabetic conditions. KEY FINDING: Diabetes significantly increased the expression of Ephrin-B2, inflammatory, and apoptotic markers in the diabetic retinas and HRP. These effects were prevented by silencing Ephrin-B2 in HRP. Moreover, Ephrin-B2 silencing in retinal pericytes decreased pathological angiogenesis and acellular capillaries formation in diabetic retinas. SIGNIFICANCE: Increased Ephrin-B2 expression in the pericytes contributed to diabetes-induced retinal inflammation and vascular death. These results identify pericytes-Ephrin-B2 as a therapeutic target for DR.


Assuntos
Apoptose , Retinopatia Diabética/metabolismo , Efrina-B2/metabolismo , Pericitos/metabolismo , Neovascularização Retiniana/metabolismo , Vasos Retinianos/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/etiologia , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Efrina-B2/deficiência , Efrina-B2/genética , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pericitos/patologia , Ratos Wistar , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Vasos Retinianos/patologia , Transdução de Sinais , Estreptozocina
15.
Life Sci ; 253: 117748, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32387415

RESUMO

AIMS: Hindlimb ischemia-reperfusion (IR) was previously demonstrated by our group to decrease blood sugar levels by suppressing hepatic gluconeogenesis and enhancing glucose uptake using activation of the parasympathetic nervous system. While IR attenuated hyperglycemia in diabetic mice, it was unclear whether IR regulated energy metabolism in the liver. We investigated the mechanisms by which IR regulates energy metabolism in the liver from type1 diabetic mice. MAIN METHODS: Streptozotocin-induced diabetic male C57BL/6J mice were used to determine the effect of IR on the factors involved in energy metabolism in the liver (i.e., activation levels of AMP-activated protein kinase, aconitase and pyruvate dehydrogenase; adenosine triphosphate and fumarate concentrations; sirtuin (Sirt) 1 expression). These various signaling pathways and key enzyme activities were examined using western blot analysis and a biochemical technique including a colorimetric assay. KEY FINDINGS: Under feeding conditions (free access to normal murine chow and water), blood glucose levels and serum ketone body levels were significantly suppressed by IR, whereas phospho-AMP-activated protein kinase and its activity, pyruvate dehydrogenase, aconitase activity, and Sirt 1expression were upregulated. In contrast, peroxisome proliferator-activated receptor γ coactivator-1, which accelerated fatty acid use, was suppressed by IR. SIGNIFICANCE: These results indicated that in the IR-treated diabetic liver, energy production was promoted through acceleration of the tricarboxylic acid cycle linked with increased glucose preference rather than fatty acid under feeding conditions. Therefore, IR may be beneficial against diabetic hyperglycemia, but also ketoacidosis.


Assuntos
Diabetes Mellitus Experimental/complicações , Cetoacidose Diabética/prevenção & controle , Precondicionamento Isquêmico , Fígado/metabolismo , Animais , Glicemia/metabolismo , Ciclo do Ácido Cítrico/fisiologia , Metabolismo Energético/fisiologia , Ácidos Graxos/metabolismo , Glicólise/fisiologia , Corpos Cetônicos/sangue , Fígado/irrigação sanguínea , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estreptozocina
16.
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
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 87-92, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376565

RESUMO

OBJECTIVE: To observe the expression of NLRP1 inflammasomes in myocardial tissues in rats with a high-fat and highsugar diet and in diabetic rats analyze the role of NLRP1 inflammasomes in the pathogenesis of diabetic cardiomyopathy. METHODS: Male SD rats were divided into normal control group, high-sugar and high-fat diet (HC) group and diabetes group. Rat models of diabetes were established by intraperitoneal injection of streptozotocin (STZ; 30 mg/kg). Serum levels of cholesterol (TC), triglyceride (TG), and fasting insulin (FINS) were measured after 8 weeks of feeding, and the insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated; Echocardiographic evaluation of cardiac structure and function was performed, and Western blotting and real-time fluorescent quantitative PCR (RT-qRCP) were used to detect the protein and mRNA expressions of NLRP1, ASC, and caspase 1 in the myocardial tissue. RESULTS: Compared with the control rats, the rats in the HC group had significantly increased body weight (BW), serum levels of TG and TC, mRNA expressions of NLRP1 and caspase 1, and the protein expression of NLRP1 (P < 0.01) without significant changes in FINS, IRI, ISI, or cardiac ultrasound findings (P > 0.05) or in myocardial ASC and caspase 1 protein expressions or serum levels of IL-1ß and IL-18 (P > 0.05). In the diabetic rats, TC, TG, and FBG levels increased and FINS, ISI decreased significantly (P < 0.01); the left ventricular end-diastolic diameter (LVID) and the left ventricular end-systolic diameter (LVSD) increased while the ejection fraction (LVEF), short axis shortening rate (FS), and E/A ratio all decreased. The expressions of NLRP1/ASC/caspase 1 pathway mRNA and NLRP1 and caspase 1 proteins also increased but myocardium ASC protein expression did not show significant changes in the diabetic rats (P > 0.05). IL-1ß and IL-18 levels were also significantly higher in the diabetic rats than in the control group (P < 0.05). Compared with those in HC group, the diabetic rats showed significantly increased serum FBG and decreased FINS, ISI and BW (P < 0.01) with decreased LVSD, LVEF and E/A ratio and increased levels of NLRP1 and caspase 1 protein expressions and serum L-1ß and IL-18 levels (P < 0.01). CONCLUSIONS: Diabetes can cause abnormal changes in cardiac structure and functions and induce inflammatory response in the myocardium, which may be related to the activation of NLRP1/ASC/ caspase 1 inflammasomes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Diabetes Mellitus Experimental/metabolismo , Inflamassomos/metabolismo , Miocárdio/metabolismo , Animais , Masculino , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Estreptozocina
18.
Life Sci ; 255: 117856, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32473246

RESUMO

BACKGROUND: Ferulic acid (FA) is a phenolic phytochemical known to protect against various diabetic complications. However, its role in diabetic neuropathy is still unclear. The present study investigated the potential protective effects of FA alone and its combination with insulin against streptozotocin (STZ)-induced diabetic neuropathy in rats. METHODS: STZ (55 mg/kg) was injected in adult Sprague-Dawley rats to induce diabetes. Diabetic rats were treated with FA (25, 50, and 100 mg/kg, p.o), insulin (10 IU/kg, s.c.) and the combination of FA (100 mg/kg, p.o.) with insulin (10 IU/kg, s.c.) for four weeks. Body weight, blood glucose, insulin, glycosylated hemoglobin, nerve conduction velocity and pain parameters were measured. Moreover, oxidative stress, inflammatory (TNF-α, IL-1ß, COX-2) and apoptotic markers (Bcl-2, Bax, caspase 3) were assessed in the sciatic nerve tissue. Na+-K+-ATPase activity and nerve growth factor (NGF) levels were also determined. RESULTS: FA attenuated STZ induced alteration in metabolic parameters, nociceptive threshold, motor nerve conduction velocity, NGF levels and Na+-K+-ATPase activity. In addition, FA boosted anti-oxidant defenses and suppressed oxidative stress, pro-inflammatory mediators and apoptotic markers. Furthermore, diabetic rats treated with insulin-FA (100 mg/kg) combination demonstrated more pronounced beneficial effects as compared to either agent alone. CONCLUSIONS: Collectively, our results suggest that FA either alone or in combination with insulin therapy could serve as an efficacious agent for treating diabetic neuropathy.


Assuntos
Ácidos Cumáricos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Animais , Antioxidantes/metabolismo , Glicemia/efeitos dos fármacos , Ácidos Cumáricos/administração & dosagem , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estreptozocina
19.
Life Sci ; 255: 117861, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32473247

RESUMO

Alzheimer's disease (AD) is closely associated with neuroinflammation development in the brain. Co-delivery of metformin (MET) with phosphatidylserine liposomes neuroprotectant may be beneficial in ameliorating AD-related symptoms like memory impairment and inflammation. Therefore, we aimed to prepare metformin containing phosphatidylserine nanoliposomes formulation (MET-PSL) and to evaluate its effect on rats subjected to AD. Alzheimer's disease model was induced by bilateral intracerebroventricular injection of streptozotocin (3 mg/kg) into rat brains using the stereotactic technique. MET-PSL, MET, and PSL alone were administered intraperitoneally to AD-induced animals and factors including learning and memory storage in addition to cytokine and tissue inflammatory changes were evaluated after a 22-day experiment period. The learning and memory parameters significantly (P < 0.05) improved in AD-rats treated with MET-PSL. Moreover, MET-PSL administration significantly (P < 0.05) decreased cytokine levels of IL1-ß, TNF-α, and TGF-ß in hippocampal tissues of rats with AD. Histological results indicated a considerable reduction in inflammatory and necrotic neural cells along with significantly (P < 0.05) increased neurogenesis in MET-PSL treated rats. Furthermore, our results showed that MET-PSL formulation could potentially act better than the free form of MET and PSL alone in the recovery process of rats with AD. In general, our data suggest that combination therapy of metformin loaded phosphatidylserine liposomes may enhance the therapeutic performance in AD patients of a clinical study.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Metformina/farmacologia , Nanopartículas , Fosfatidilserinas/química , Doença de Alzheimer/fisiopatologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Hipocampo/patologia , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Lipossomos , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/fisiopatologia , Ratos , Ratos Wistar , Estreptozocina
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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