Modification of cardiac oxidative stress in alloxan-induced diabetic rabbits with repaglinide treatment.
The aim of this study was to analyze the antioxidative effect of repaglinide in the heart of alloxan-induced diabetic rabbits. The activities of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), products of lipid peroxidation (LPO) and protein carbonyl groups (PCG) were estimated after 4 and 8 weeks of repaglinide treatment (1 mg daily). At significance level p<0.05, in diabetic heart the activities of Cu,Zn-SOD and CAT were elevated as compared to control values (by 60.7% and 55.3% for Cu,Zn-SOD, and by 89.7% and 77.4% for CAT after 4 and 8 weeks, respectively). The level of AA was diminished by 52.5% and 41.5% while GSH-Px and GSSG-R activities were decreased after 4 weeks of experiment (by 11.5% and 14.4%, respectively). GSH level was diminished by 33.2% after 8 weeks. Simultaneously, in diabetic heart the levels of LPO and PCG were elevated as compared to control values (by 51.6% and 111.3% for LPO, and by 72.0% and 132.9% for PCG after 4 and 8 weeks, respectively). In diabetic animals, repaglinide normalized GSH-Px activity and GSH level. It modified the activities of Cu,Zn-SOD, CAT and AA as compared to diabetic non-treated animals. In diabetic-treated rabbits the level of LPO was diminished as compared to diabetic non-treated animals, while the level of PCG was not affected. In the present study, repaglinide did not affect blood glucose and plasma insulin concentrations in diabetic rabbits. Nevertheless, the drug showed some beneficial antioxidative properties in the heart tissue.
Gumieniczek
Anna
A
Medical University of Lublin, Department of Medicinal Chemistry, Jaczewskiego Str. 4, 20-090 Lublin, Poland. anna.gumieniczek@am.lublin.pl
D000496:Alloxan; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits
D000975:Antioxidants; D001786:Blood Glucose; D002219:Carbamates; D007328:Insulin; D010880:Piperidines; C072379:repaglinide; D000496:Alloxan