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
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.