Effects of repaglinide on oxidative stress in tissues of diabetic rabbits

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 (0.3 mg/kg daily). In liver, diabetic versus control values (mean ± S.E.M., p < 0.05) for GSH-Px were 181.0 ± 5.4 mU/mg protein versus 203.1 ± 1.9 mU/mg protein and 187.4 ± 6.6 mU/mg protein versus 240.9 ± 18.8 mU/mg protein. The respective values for GSH were 33.7 ± 0.4 nmol/mg protein versus 49.0 ± 1.6 nmol/mg protein and 37.7 ± 1.0 nmol/mg protein versus 41.2 ± 0.7 nmol/mg protein. In diabetic kidney, GSSG-R activity (20.6 ± 1.6 mU/mg protein versus 32.4 ± 1.5 mU/mg protein and 23.6 ± 0.6 mU/mg protein versus 36.3 ± 0.3 mU/mg protein) and GSH level (16.6 ± 0.5 nmol/mg protein versus 23.2 ± 0.9 nmol/mg protein and 17.9 ± 0.5 nmol/mg protein versus 23.2 ± 0.6 nmol/mg protein) were reduced compared to control. PCG level was elevated in diabetic liver (0.58 ± 0.02 nmol/mg protein versus 0.16 ± 0.03 nmol/mg protein at 4 weeks and 0.64 ± 0.04 nmol/mg protein versus 0.16 ± 0.03 nmol/mg protein at 8 weeks) and in diabetic kidney (0.32 ± 0.03 nmol/mg protein versus 0.11 ± 0.02 nmol/mg protein and 0.35 ± 0.03 nmol/mg protein versus 0.16 ± 0.03 nmol/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 ± 2.0 mU/mg protein at 4 weeks and 41.1 ± 0.07 mU/mg protein at 8 weeks), GSH level (27.0 ± 0.8 and 26.8 ± 0.9 nmol/mg protein), and partly PCG level (0.17 ± 0.02 nmol/mg protein at 8 weeks). The treatment partly affected GSH-Px activity (262.7 ± 17.6 mU/mg protein) and GSH level (40.4 ± 1.4 nmol/mg protein) in diabetic liver. This study shows that repaglinide produces measurable antioxidative effects at therapeutic dose.