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

Citation
S. Tuzun et al., Antioxidant status in experimental type 2 diabetes mellitus: effects of glibenclamide and glipizide on various rat tissues, EXP TOX PAT, 51(4-5), 1999, pp. 436-441
Citations number
26
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY
ISSN journal
09402993 → ACNP
Volume
51
Issue
4-5
Year of publication
1999
Pages
436 - 441
Database
ISI
SICI code
0940-2993(199907)51:4-5<436:ASIET2>2.0.ZU;2-7
Abstract
The well known animal models are not satisfactory in reproducing the essent ials of human type 2 diabetes. A recent experimental model successful in pr oducing 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 > IOmm ol/L). The first group (n = 8) did not receive any medication, glibenclamid e 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, th e levels of Malondialdehyde (MDA) a lipid peroxidation marker, and the acti vity of catalase (CAT), an antioxidant enzyme, were determined in various t issues in all of the diabetic groups compared to the controls (n = 8, gluco se 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 grou p (12,6 +/- 4U/mg protein) compared to the control (7,9 +/- 1,8 U/mgprot) a nd 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 s ignificant 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 glip izide (75,1 +/- 20 U/mgprot) restored CAT activity. CAT activity of the con trol 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 t issue CAT activity in diabetic rats (p < 0.05). MDA levels showed a significant elevation in all tissues both in the untrea ted diabetics and drug treated groups (p < 0,01). Brain tissue being an exc eption, MDA levels manifested a significant decrease in both of the drug ad ministered groups; as compared to the untreated diabetes (glibenclamide tre ated 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 i n the treated and untreated groups in type 2 diabetes, we noted that in lun g 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 cha nges could be noted on other tissues. As tissue antioxidant status is an important Factor in the etiology of diab etes and its complications, treatment by glipizide and glibenclamide may pl ay a prominant role in scavenging free radicals and restoring antioxidant a ctivity.