Protective effects of enalapril in streptozotocin-induced diabetic rat: studies of DNA damage, apoptosis and expression of CCN2 in the heart, kidney and liver.

Abstract

Diabetes mellitus is characterized by hyperglycemia, which induces oxidative stress and perturbs a number of pathways, leading to tissue injury. One of the pathological responses to tissue injury is the development of fibrosis and cell death. Enalapril is a non-thiol angiotensin-converting enzyme inhibitor that is commonly used in the treatment of diabetes-associated hypertension. The present study examines the possible beneficial effects of enalapril on the development of diabetes associated fibrosis and DNA damage in rats. Sprague-Dawley rats (250 ± 10 g) were used in the study. Enalapril (10 mg kg(-1) per oral) was administered for four consecutive weeks to the streptozotocin (STZ)-induced diabetic rats. After 4 weeks, all the animals were sacrificed and comet assay (normal and modified) was performed to detect the normal as well as oxidative DNA damage. Expression of profibrotic marker CCN2 and fibrosis was examined in the heart, kidney and liver of diabetic rats. Enalapril treatment significantly restored the malondialdehyde and glutathione content as well as the DNA damage in the heart, kidney and liver of diabetic rat. Significant decrease in the expression of CCN2 was observed in the heart, kidney and liver of diabetic rat receiving enalapril treatment as compared with the diabetic group. Further, the enalapril treatment led to significant decrease in the fibrosis and CCN2 expression in the diabetic group as compared with control. The results of the present study clearly demonstrate that enalapril ameliorates the DNA damage, cell death and expression of CCN2 in the heart, kidney and liver of the STZ-induced diabetic rat.

• Authors: S Kushwaha, A Vikram, G B Jena
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 32 Issue 9 Pg. 662-72 (Sep 2012) ISSN: 1099-1263 [Electronic] England
• PMID: 21416479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• CCN2 protein, human
• Connective Tissue Growth Factor
• Streptozocin
• Enalapril

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Apoptosis (drug effects)
• Comet Assay
• Connective Tissue Growth Factor (metabolism)
• DNA Damage (drug effects)
• Diabetes Mellitus, Experimental (drug therapy, genetics, metabolism, pathology)
• Enalapril (pharmacology)
• Fibrosis (chemically induced, drug therapy, metabolism, pathology)
• Heart (drug effects)
• Kidney (drug effects, metabolism, pathology)
• Liver (drug effects, metabolism, pathology)
• Male
• Myocardium (metabolism, pathology)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Streptozocin