Effects of pioglitazone on hyperglycemia-induced alterations in antioxidative system in tissues of alloxan-treated diabetic animals

Hyperglycemia not only generates reactive oxygen species but also attenuates antioxidant mechanisms creating a state of oxidative stress. Oxidative stress is thought to play a crucial role in pathogenesis of chronic diabetic complications. Pioglitazone is a new oral antidiabetic agent, a potent inhibitor of glycation and potent antioxidant. In the present study, normoglycemic and alloxan-induced diabetic rabbits were treated with pioglitazone (1 mg/kg daily) for 4 and 8 weeks. At the end, glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH) and protein carbonyl groups (PCG) were evaluated in homogenates of liver and kidney. Chronic hyperglycemia caused a marked increase in oxidative processes and some changes in activity of antioxidants. In liver, diabetic vs. control values (mean±S.E.M; P<0.05) for GSH-Px were 181.0±5.4 vs. 203.1±1.9 and 187.4±6.6 vs. 240.9±18.8 mU/mg protein. Pioglitazone treatment for 8 weeks affected GSH-Px activity in diabetic liver (261.5±7.3 mU/mg protein). In diabetic kidney, GSSG-R activity (20.6±1.6 vs. 32.4±1.5 and 23.6±0.6 vs. 36.3±0.3 mU/mg protein) and GSH level (16.6±0.5 vs. 23.2±0.9 and 17.9±0.5 vs. 23.2±0.6 nmol/mg protein) were diminished, while PCG level (0.32±0.03 vs. 0.11±0.02 and 0.35±0.03 vs. 0.16±0.03 nmol/mg protein) was elevated. In diabetic kidney, pioglitazone restored to control values GSSG-R activity (34.4±1.4 and 30.6±0.1 mU/mg protein) as well as GSH (25.5±1.2 and 21.6±0.5 nmol/mg protein) and PCG (0.16±0.01 and 0.19±0.02 nmol/mg protein) levels. The present study showed that pioglitazone reduced to some extent the oxidative stress enhanced by chronic hyperglycemia.