Pentoxifylline decreases glycemia levels and TNF-alpha, iNOS and COX-2 expressions in diabetic rat pancreas

Abstract

Pentoxifylline (PTX), a methyl xanthine derivative, is a phosphodiesterase inhibitor with anti-inflammatory and renoprotective effects in diabetic patients, among other properties. We studied PTX actions and mechanisms in reducing blood biochemical parameters, in diabetic rats. For diabetes induction, alloxan was intravenously administered to male Wistar rats. One group was left untreated and the other ones treated with PTX (25, 50 and 100 mg/kg), glibenclamide or metformin, as references. Forty-eight hours later and after 1-week to 3-month treatments, blood was collected for determination of glycemia, triglycerides, cholesterol, transaminases, fructosamine and glycated hemoglobin. Afterwards, the animals were euthanized and pancreas, liver and kidney processed for histological analyses and immunohistochemistry assays for TNF-alpha, iNOS and COX-2. The results showed that PTX decreased glycemia and also triglyceride levels, starting 1 week after treatments, as compared to the same group before treatments. Glycemia values were brought towards normality, after 1-month treatment. PTX hypoglycemic effects were potentiated by glibenclamide but not by metformin. It also decreased fructosamine and glycated hemoglobin. Some histological and immunohistochemical alterations for TNF-alpha, iNOS and COX-2 in the diabetic pancreas were also reversed by PTX. We conclude that PTX acts similarly to glibenclamide, and its hypoglycemic actions are, partly, a consequence of ATP-sensitive K+ channels inhibition. In addition, by its anti-inflammatory and antioxidant properties, PTX may be a therapeutic alternative for the treatment of diabetes and its complications.