Minocycline decreases blood glucose and triglyceride levels and reverses histological and immunohisto-chemical alterations in pancreas, liver and kidney of alloxan-induced diabetic rats

Abstract

Increasing evidence suggests that oxidative stress and inflammation play major roles in diabetes mellitus and its complications. Furthermore, hyperglycemia increases the production of free radicals, resulting in oxidative stress. Minocycline presents potent anti-inflammatory and antioxidant activities, as evaluated by in vivo and in vitro models. In the present study, the minocycline anti-diabetic effect was assessed in the model of alloxan-induced diabetes. Alloxan was injected to male Wistar rats (50 mg/kg, intravenously), and their blood was collected 48 h later and also after treatments, for measurements of glycemia, triglycerides, cholesterol and liver transaminases. Groups of untreated diabetic controls and diabetic treated with minocycline (1 to 50 mg/kg, peritoneally, p.o.) or glibenclamide (5 mg/kg, p.o., as reference), for different periods, were used. Furthermore, slices of pancreas, liver and kidney were submitted to histological and immunohistochemical analyses. While significant decreases in glucose and triglycerides were shown at the 5th and mainly at the 30th days after minocycline treatments, as compared to the untreated diabetic group, no changes were observed in total cholesterol, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels. Histological analyses of pancreas, liver and kidney showed that minocycline significantly reversed tissue alterations, as those seen in untreated diabetic animals. Besides, minocycline also reduced tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expressions. The beneficial minocycline effects in diabetes could be due, at least partly, to its antiinflammatory and antioxidant properties, indicating that this drug may be a therapeutic alternative in diabetes mellitus and other pathological conditions where inflammation plays a significant role.