Written by International Journal of Pharmacology and Clinical Sciences, 2015, 4, 4, 76-82.
DOI: 10.5530/ijpcs.4.4.2
Published: December 2015
Type: Research Article
Authors: Vandana Shamrao Nade*, Pranita Pradip Dharmadhikari, Laxman Ashok Kawale
Author(s) affiliations:
Vandana Shamrao Nade*, Pranita Pradip Dharmadhikari, Laxman Ashok Kawale
Department of Pharmacology, M.V.P. Samaj’s College of Pharmacy, Gangapur Road, Nashik, Maharashtra-422002, INDIA.
Abstract
Background: Angiotensin receptor blockers are the new class of compounds used for the treatment of fibrotic diseases. Objectives: The purpose of this study was to investigate the cardioprotective effect of irbesartan in isoproterenol-induced endoplasmic reticulum stress, which results in myocardial fibrosis. Materials and Methods: Thirty Wistar rats were assigned to the study, with 6 rats in each group. Myocardial fibrosis was induced by isoproterenol (5 mg/kg, s.c. for 15 days) which can cause cardiac toxicity. Irbesartan (10, 20, and 30 mg/kg, p.o.) was administered for 15 days after administration of isoproterenol. Post-treatment with irbesartan, cardiac functional measurements and the left and right ventricular weight indices were analyzed. Pathological alteration of levels of soluble collagen was determined. Results: The administration of irbesartan resulted in a significant (p<0.01) improvement in cardiac function and reduced levels of soluble collagen. Irbesartan also showed a decrease in the level of malondialdehyde and an increase in defensive antioxidant enzymes (SOD, CAT, and GSH), thus exerting antioxidant activity. Conclusion: Irbesartan possesses anti-fibrotic activity and offers protection against myocardial fibrosis, due to the regulation of angiotensin II activity through the blockade of AT1 receptors which might attenuate the endoplasmic reticulum stress and thus inhibit myocardial fibrosis via the inhibition of oxidative stress. The regulation of antioxidant defensive enzymes may be involved in the anti-fibrotic effect of irbesartan.
Keywords: Endoplasmic Reticulum Stress, Irbesartan, Isoproterenol, Myocardial Fibrosis, Oxidative Stress, Soluble Collagen