Antioxidant status in experimental type 2 diabetes mellitus: effects of glibenclamide and glipizide on various rat tissues

16th European Workshop on Drug Metabolism -- JUN 21-26, 1998 -- COPENHAGEN, DENMARKWOS: 000082403000033PubMed ID: 10445412The well known animal models are not satisfactory in reproducing the essentials of human type 2 diabetes. A recent experimental model successful in producing type 2 diabetes in rats is induced by neonatal streptozotocin (STZ) administration. In the present study, diabetes was accomplished in rats by the intraperitoneal injection of STZ (65 mg/kg) on the second day of birth. Blood glucose levels were monitored until the fourth month. At the fourth month, diabetic rats were divided into three groups (glucose levels > IOmmol/L). The first group (n = 8) did not receive any medication, glibenclamide and glipizide were administered respectively to the second group (n = 8; 5 mg/kg bw) and third group (n = 8; 5 mg/kg bw) for a one month period. In order to observe the antioxidant effects of glibenclamide and glipizide, the levels of Malondialdehyde (MDA) a lipid peroxidation marker, and the activity of catalase (CAT), an antioxidant enzyme, were determined in various tissues in all of the diabetic groups compared to the controls (n = 8, glucose levels similar to 6 mmol/L). CAT activities and MDA levels were performed by the modified method of Aebi and Okhawa, respectively in lung, cardiac, brain, liver and renal tissues. Diabetic CAT activity was found to be decreased in liver tissue (p < 0,01). After glipizide administration, CAT activity was normalized (p < 0,01) in the liver while the values found after glibenclamide treatment did not show any statistically significant change. In lung tissue, CAT activity showed a significant increase in diabetic group (12,6 +/- 4U/mg protein) compared to the control (7,9 +/- 1,8 U/mgprot) and glibenclamide treated groups (8,7 +/- 3,3 U/mgprot) (p < 0,03).The lung tissue of the glipizide group (9,6 +/- 2,5 U/mgprot) did not manifest any significant variation with respect to group 1. In rat kidney, CAT activities were significantly decreased in group 1 (40,5 +/- 11 U/mgprot) (p < 0.002). However administration of glibenclamide (98,3 +/- 39,5 U/mgprot) and glipizide (75,1 +/- 20 U/mgprot) restored CAT activity. CAT activity of the control group was 81,4 +/- 28,4 U/mg prot in renal tissue. In cardiac tissue, CAT activity was significantly higher in the untreated diabetic group (12,6 +/- 4 U/mgprot) as compared to the controls (6,5 +/- 1U/mgprot) (p < 0,001). Glibenclamide treatment (8,8 +/- 1U/mgprot) markedly decreased cardiac tissue CAT activity in diabetic rats (p < 0.05). MDA levels showed a significant elevation in all tissues both in the untreated diabetics and drug treated groups (p < 0,01). Brain tissue being an exception, MDA levels manifested a significant decrease in both of the drug administered groups; as compared to the untreated diabetes (glibenclamide treated 78,4 +/- 15 nmol/gr weight tissue; glipizide treated 73,7 +/- 18 nmol/gr weight tissue, untreated group 108 +/- 22 nmol/gr weight tissue, control group 54,2 +/- 12 nmol/gr weight tissue) (p < 0,001). Comparing the effects of glibenclamide and glipizide on cataIase activity in the treated and untreated groups in type 2 diabetes, we noted that in lung and heart tissues glibenclamide, in renal tissue both of the drugs had a significant effect on catalase activity. The changes in MDA levels in brain showed that gIipizide and glibenclamide treatment restored lipid peroxidation in this tissue. However no marked changes could be noted on other tissues. As tissue antioxidant status is an important Factor in the etiology of diabetes and its complications, treatment by glipizide and glibenclamide may play a prominant role in scavenging free radicals and restoring antioxidant activity.European Soc Biochem Pharmaco