Oxidative stress in kidney and liver of alloxan-induced diabetic rabbits: effect of repaglinide.
The aim of this study was to analyse the effect of the new oral antidiabetic drug repaglinide on antioxidant factors and lipid peroxidation in tissues of alloxan-induced diabetic rabbits after 4 and 8 weeks treatment. The activity of superoxide dismutase (diabetic vs. control values, mean+/-S.E.M., p<0.05) in diabetic kidney was diminished (1.5+/-0.2 vs. 2.8+/-0.3 and 1.8+/-0.1 vs. 2.9+/-0.3 U/mg protein) and significantly increased after 8 weeks of repaglinide treatment (2.4+/-0.2 U/mg protein). Catalase activity was significantly increased in diabetic liver (67.5+/-3.6 vs. 39.7+/-5.6 and 62.3+/-2.7 vs. 52.6+/-5.3 micromol H(2)O(2)/min/mg protein) and normalised by repaglinide (49.2+/-4.0 and 41.2+/-3.8 micromol H(2)O(2)/min/mg protein). In diabetic kidney the level of ascorbic acid was diminished after 4 weeks (1.5+/-0.1 vs. 3.0+/-0.1 micromol/g tissue) and increased after the drug treatment (2.0+/-0.2 micromol/g tissue). In diabetic kidney the level of lipid peroxidation products was elevated (33.3+/-2.4 vs. 23.7+/-2.4 and 29.5+/-3.1 vs. 18.2+/-0.8 nmol/g tissue) and diminished by repaglinide (10.3+/-1.4 and 13.3+/-3.0 nmol/g tissue). This study shows that oxidative stress in diabetic tissues is partly corrected by repaglinide. The drug does not affect glucose concentration and its antioxidative effect is not secondary to its action on hyperglycaemia. This study suggests an additional advantage of repaglinide which contributes to its effectiveness in therapy.
Gumieniczek
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Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Poland. anna.gumieniczek@am.lublin.pl
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002219:Carbamates / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000502:physiology*; D010880:Piperidines / Q000627:therapeutic use*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000378:metabolism
D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide; D002374:Catalase; D013482:Superoxide Dismutase