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.
Gumieniczek
Anna
A
Department of Medicinal Chemistry, Medical University of Lublin, Chodzki Street 6, 20-093 Lublin, Poland. gumieni@asklepios.am.lublin.pl
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D013997:Time Factors
D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase