The Effect of Rosiglitazone, a Peroxisome Proliferator-Activated Receptor Gamma Agonist, in Alloxan-Induced Diabetic Rats.
Behr, G.A.1; Da Silva, E.G.1; Lorenzi, R.1; Pasquali, M.A.B.1; Streck, E.L.2; Dal-Pizzol, F.3; Moreira, J.C.F.1
1 Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, RS; 2 Laboratório de Bioquímica Experimental, Universidade do Extremo Sul Catarinense, SC; 3 Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, SC. Brazil.
The thiazolidinediones including rosiglitazone (RGZ) acts as insulin sensitizers attenuating hyperglycemia, hyperinsulinemia and dyslipidemia in type II diabetes mellitus (TIIDM) patients, thereby decreasing the risk of cardiovascular disease associated with insulin resistance. The aim of this study was to evaluate the effectiveness of RGZ, a commonly administered drug for TIIDM, in an animal model of type I diabetes mellitus (TIDM) induced by alloxan. Animals were randomly divided into two groups: non-induced and diabetic-induced. Diabetes was induced by an intraperitoneal injection of 150 mg/kg of alloxan monohydrate (0.9% NaCl) after overnight fasting. Non-induced group received only 0.9% NaCl. Blood glucose levels were monitored thereafter by blood glucose monitor (Accu-Chek® Active blood glucose monitor). After ten days animals from the diabetic-induced group, which have exhibited glucose levels lower than 300 mg/dL, were not used in this study. Non-induced and diabetic-induced groups were once more randomly subdivided into two subgroups each. These were treated for 20 days with a single intragastric dose per day of rosiglitazone maleate (3 mg/Kg) or saline (0.9% NaCl). RGZ decreased blood glucose in diabetic-induced group (from 558.03 ± 60.56 mg/dL before treatment to 294.4 ± 42.74 mg/dL after treatment) and increased body weight significantly in diabetic-induced group (16.04 ± 4.56 %) when compared to diabetic-induced untreated group (2.14 ± 6.29 %). We observed a significant decrease in HbA1C levels in diabetic-induced RGZ-treated group (3.46 %) when compared to diabetic-induced untreated group (4.29 %). RGZ treatment reduces glycogen content in heart and kidney (2.41 ± 0.31 and 0.41 ± 0.29 mg/%) in diabetic–induced group when compared to diabetic-induced untreated group (3.28 ± 0.28 and 2.21 ± 0.21 mg/%) respectively. RGZ treatment did not increase hepatic transaminase (AST and ALT) and Glutathione S-transferase. RGZ treatment decreased C-reactive protein level (6.0 ± 0.5 mg/L) compared to diabetic-induced untreated rats (9.7 ± 1.8 mg/L). Taken into account these results suggest that RZG may be particularly considered for trials aiming TIDM treatment. Financial support: CNPq, Fapergs and Propesq/UFRGS.
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