Effects of repaglinide on oxidative stress in tissues of diabetic rabbits

Abstract 

In this study, the antioxidative properties of repaglinide were examined in tissues of alloxan-induced diabetic rabbits. Glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and protein carbonyl groups (PCG) were measured after 4 and 8 weeks treatment with repaglinide (0.3mg/kg daily). In liver, diabetic versus control values (mean±S.E.M., p<0.05) for GSH-Px were 181.0±5.4mU/mg protein versus 203.1±1.9mU/mg protein and 187.4±6.6mU/mg protein versus 240.9±18.8mU/mg protein. The respective values for GSH were 33.7±0.4nmol/mg protein versus 49.0±1.6nmol/mg protein and 37.7±1.0nmol/mg protein versus 41.2±0.7nmol/mg protein. In diabetic kidney, GSSG-R activity (20.6±1.6mU/mg protein versus 32.4±1.5mU/mg protein and 23.6±0.6mU/mg protein versus 36.3±0.3mU/mg protein) and GSH level (16.6±0.5nmol/mg protein versus 23.2±0.9nmol/mg protein and 17.9±0.5nmol/mg protein versus 23.2±0.6nmol/mg protein) were reduced compared to control. PCG level was elevated in diabetic liver (0.58±0.02nmol/mg protein versus 0.16±0.03nmol/mg protein at 4 weeks and 0.64±0.04nmol/mg protein versus 0.16±0.03nmol/mg protein at 8 weeks) and in diabetic kidney (0.32±0.03nmol/mg protein versus 0.11±0.02nmol/mg protein and 0.35±0.03 nmol/mg protein versus 0.16±0.03nmol/mg protein). Repaglinide did not affect the glucose level but reduced to some extent the oxidative stress enhanced by chronic hyperglycemia. In diabetic kidney, it restored to control values GSSG-R activity (45.4±2.0mU/mg protein at 4 weeks and 41.1±0.07mU/mg protein at 8 weeks), GSH level (27.0±0.8 and 26.8±0.9nmol/mg protein), and partly PCG level (0.17±0.02nmol/mg protein at 8 weeks). The treatment partly affected GSH-Px activity (262.7±17.6mU/mg protein) and GSH level (40.4±1.4nmol/mg protein) in diabetic liver. This study shows that repaglinide produces measurable antioxidative effects at therapeutic dose.

Keywords: Repaglinide, Oxidative stress, Diabetes, Rabbits