Effect of carvedilol on some diabetic complications in rats

Howaida Saber Salama

Mahmoud H. Abdel -Raheem,Eman M. Zaki,Safaa Y. Salim

Abstract:
The main objective of the present study is to evaluate the pharmacological effects of the single and combined

administration of carvedilol and vitamin E in STZ-induced diabetic nephropathy and cardiomyopathy in rats.
To achieve this goal we investigated the effects of the tested drugs on: a) the biochemical changes (blood glucose
level, lipid profile, serum levels of MAD and TAOS, renal function tests, CPK b) The expression of Bcl-2 protein in
kidney and heart tissues c) The histopathological changes in kidney and heart tissues in diabetic nephropathy and
cardiomyopathy induced in adult male Wistar albino rats by STZ.
Our results revealed that:
1-Carvedilol and vitamin E treatments were found to be effective in increasing the body weight loss associated with
STZ- induced diabetes in rats.
2- Treatment of vitamin E alone and combined with carvedilol are effective in decreasing hyperglycemia of STZinduced diabetes in rats. However, treatment with carvedilol alone did not affect blood glucose level.
3- Carvedilol and vitamin E treatments were found to be effective in treatment of dyslipedemia associated STZinduced diabetes in rats.
4- Carvedilol and vitamin E treatments as antioxidants which decreased the lipid peroxidation (MAD) and increased
the TAOS in STZ- induced diabetes in rats.
5- Carvedilol and vitamin E treatments corrected the renal function tests and cardiac enzyme serum level in STZinduced diabetes in rats.
6- Carvedilol and vitamin E treatments enhanced the expression of antioxidant and anti-apoptotic Bcl-2 protein in
the cardiac and renal tissues in STZ- induced diabetes in rats.
7- Carvedilol and vitamin E treatments improved the histopathological changes on the cardiac and renal tissues of
STZ- induced diabetes in rats.
8-The beneficial effects of carvedilol seemed to be remarkably augmented following the combined administration of
vitamin E.
The possible mechanisms by which these drugs exert their effects in STZ-diabetic rats could be attributed to the fact
that a carbazole moiety in carvedilol chemical structure and its metabolites display potent antioxidant activity, which
may include the followings: (1) inhibiting electron adduction by 5,5-dimethylpyrroline-1-oxide and 2-methylnitrosopropane, (2) inhibiting lipid peroxidation in both renal and myocardial cell membranes, (3) inhibiting release
of O2 through neutrophils, (4) preserving the natural antioxidant systems of the body (i.e., vitamin E and
glutathione), (5) scavenging peroxy and hypochlorous radicals, and (6) performing other system protective functions
based on the reduction of free radicals. Moreover, carvedilol enhances the expression of antioxidant and antiapoptotic Bcl-2 protein and increasing the TAOS in the serum.
Vitamin E, as a powerful antioxidant, corrects oxidative stress that is implicated in the pathogenesis of diabetic
cardiomyopathy and nephropathy by inducing cardiovascular defects that result in endocardial and renal hypoxia
and subsequent cardiac and renal dysfunction. Furthermore, vitamin E treatment via controlling hyperglycemia has
possibly decreases the oxidative stress and thus, led to the prevention and/or curing of diabetic complication
including cardiomyopathy and dyslipedemia.
In addition, the greater antioxidant effect of carvedilol and vitamin E may be important in improving cardiovascular
diabetic complications.
Conclusion
In sum, oxidative stress was involved in the early diabetic cardiac and renal dysfunction that not only led to reduce
total antioxidant status but also subdued cardiac and renal dysfunction. Carvedilol and vitamin E treatments
upregulated expression of Bcl-2 protein, increased the total antioxidant status and improved cardiac and renal
functions. Our study indicated that carvedilol and vitamin E were beneficial to hearts and kidney of early diabetic
rats due partly at least to their antioxidant property.
Finally, we consider that this study should be followed by further thorough studies to elucidate the mechanism of
actions of carvedilol usefulness in other different diabetic complications and trial to clinical study.

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