Protective effects of epicatechin against the toxic effects of streptozotocin on rat pancreatic islets: in vivo and in vitro.
ABSTRACT Green tea catechins have diverse pharmacological effects such as anticarcinogenic and antioxidant activities.
To study the protective effects of green tea (-)-epicatechin (EC) against the toxic effects of streptozotocin (STZ), a selective beta cell toxin, on pancreatic islets in vivo and in vitro.
Rats were randomly divided into four groups: control, EC (30 mg/kg)-treated, STZ (60 mg/kg)-treated, and EC plus STZ (same doses; EC+STZ)-treated rats. EC was administered twice a day for 6 days, and a single injection of STZ was used. In EC+STZ-treated rats, EC was administered 6 hours prior to STZ since posttreatment with EC had no beneficial effects on fully developed diabetes in our unpublished study. Insulin and insulin mRNA were detected by immunohistochemical analysis and in situ hybridization, respectively, and physiologic parameters including blood glucose concentration were measured daily. Following isolation of the islets, insulin release, nitrite levels, and islet morphology were observed in the four groups: control, EC (0.8 mM)-treated, STZ (5 mM)-treated, and EC+STZ (same doses)-treated islets.
In EC+STZ-treated rats, hyperglycemia and weight loss were not observed and islet morphology was well preserved compared with STZ-treated rats. Compared with STZ treatment alone, insulin release was increased and nitrite production was decreased in EC+STZ-treated islets.
EC appears to be helpful in protecting pancreatic islets against exposure to STZ in both in vivo and in vitro systems.
SourceAvailable from: Isabel Cordero Herrera[Show abstract] [Hide abstract]
ABSTRACT: Insulin resistance is the primary characteristic of type 2 diabetes. Cocoa and its main flavanol, (-)-epicatechin (EC), display some antidiabetic effects, but the mechanisms for their preventive activities related to glucose metabolism and insulin signalling in the liver remain largely unknown. In the present work, the preventive effect of EC and a cocoa polyphenolic extract (CPE) on insulin signalling and on both glucose production and uptake are studied in insulin-responsive human HepG2 cells treated with high glucose. Pre-treatment of cells with EC or CPE reverted decreased tyrosine-phosphorylated and total levels of IR, IRS-1 and -2 triggered by high glucose. EC and CPE pre-treatment also prevented the inactivation of the PI3K/AKT pathway and AMPK, as well as the diminution of GLUT-2 levels induced by high glucose. Furthermore, pre-treatment of cells with EC and CPE avoided the increase in PEPCK levels and the diminished glucose uptake provoked by high glucose, returning enhanced levels of glucose production and decreased glycogen content to control values. These findings suggest that EC and CPE improved insulin sensitivity of HepG2 treated with high glucose, preventing or delaying a potential hepatic dysfunction through the attenuation of the insulin signalling blockade and the modulation of glucose uptake and production.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2013; 64. DOI:10.1016/j.fct.2013.11.014 · 2.99 Impact Factor
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ABSTRACT: Background: Myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow was reported in ischemic (IS) and nonischemic (NIS) hemispheres after stroke. Ischemia/reperfusion injury and resulting oxidative stress impair myogenic response in IS hemisphere. Yet, the mechanism by which ischemia/reperfusion affects the NIS side is still undetermined. Goal: to determine the effect of ischemia/reperfusion injury on the myogenic reactivity of cerebral vessels from both hemispheres, and whether protein nitration due to excess peroxynitrite production is the underlying mechanism of loss of tone. Methods: Male Wistar-rats were subjected to sham or 30 min middle-cerebral-artery (MCA) occlusion/45 min reperfusion. Rats were administered saline, peroxynitrite decomposition catalyst FeTPPs or nitration inhibitor epicatechin at reperfusion. MCAs isolated from another set of control rats were exposed to ex-vivo oxygen-glucose- deprivation (OGD) with & without gp-91 tat (NOX inhibitor) or L-NAME. Myogenic tone and nitrotyrosine levels were determined. Results: Ischemia/reperfusion injury impaired myogenic tone of vessels in both hemispheres compared to sham (***p<0.001). Vessels exposed to ex-vivo OGD experienced similar loss of myogenic tone. Inhibiting peroxynitrite parent radicals significantly improved myogenic tone. Scavenging peroxynitrite or inhibiting nitration improved myogenic tone of vessels from IS (***p<0.001,*p<0.05 respectively) and NIS hemispheres (**p<0.01, *p<0.05 respectively). Nitration was significantly increased in both hemispheres vs sham and was normalized with epicatechin treatment. Conclusion: Ischemia/reperfusion injury impairs vessel reactivity in both hemispheres via nitration. We suggest that sham animals rather than nonischemic side should be used as a control in preclinical stroke studies.AJP Heart and Circulatory Physiology 10/2013; 305(12). DOI:10.1152/ajpheart.00535.2013 · 4.01 Impact Factor
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ABSTRACT: Diabetes mellitus is a major metabolic disorder affecting a huge population all over the world. Artemisia species have been extensively used for the management of diabetes in folkloric medicine. The present study was designed to investigate the antidiabetic and antihyperlipidemic effects of aeriel parts of Artemisia indica. Hydromethanolic crude extracts, chloroform, ethyl acetate and n-butanol fractions of aerial parts of Artemisia indica were tested for their antidiabetic potential in Streptozotocin (STZ) (50mg/kg. i.p) induced diabetic Sprague Dawley rats. Blood glucose level, body weight, serum lipid profile and activities of liver enzymes were determined. The extracts were further subjected to preliminary phytochemical analysis. A daily oral dose of hydromethanolic crude extracts (200 and 400mg/kg b.w) and chloroform fraction (200mg/kg b.w) of Artemisia indica for 15 days showed a significant reduction in blood glucose level which was comparable to the standard antidiabetic drug, glibenclamide (500μg/kg, p.o). Artemisia indica extracts also showed reduction in total cholesterol, triglycerides and low density lipoproteins as well as serum creatinine level, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and alkaline phosphatase (ALP) in diabetic rats. According to results Artemisia indica possesses hypoglycemic, antihyperlipidemic and valuable effects on liver and renal functions in diabetic rats, which seems to validate its traditional usage.Journal of ethnopharmacology 11/2013; DOI:10.1016/j.jep.2013.11.012 · 2.32 Impact Factor