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Effect of mast cell stabilizers in hyperhomocysteinemia-induced cardiac hypertrophy in rats.

Abstract：

BACKGROUND:The present study has been designed to investigate the effect of sodium cromoglycate and ketotifen, mast cell stabilizers in hyperhomocysteinemia-induced cardiac hypertrophy in rats. METHODS:Rats were administered L-methionine (1.7 g/kg/day PO) for 8 weeks to produce hyperhomocysteinemia. Sodium cromoglycate (24 mg/kg/day IP) and ketotifen (1mg/kg/day IP) treatments were started from first day of administration of L-methionine and continued for 8 weeks. The development of cardiac hypertrophy was assessed in terms of measuring mean arterial blood pressure (MABP), ratio of left ventricular (LV) weight to body weight (LVW/BW), LV wall thickness (LVWT), LV protein content, and LV collagen content. Further, the oxidative stress in heart was assessed by measuring lipid peroxidation, superoxide anion generation, and reduced glutathione (GSH). Moreover, the cardiomyocyte diameter and LV mast cell density were determined using hematoxylin-eosin and toluidine blue staining, respectively. RESULTS:The L-methionine administration produced hyperhomocysteinemia, which significantly increased MABP, oxidative stress, and density of mast cells and consequently produced cardiac hypertrophy by increasing cardiomyocyte diameter, LVW/BW, LVWT, LV protein and collagen content. However, sodium cromoglycate and ketotifen treatments significantly attenuated hyperhomocysteinemia-induced oxidative stress and pathological cardiac hypertrophy without significantly altering MABP. Moreover, sodium cromoglycate and ketotifen treatments did not affect serum homocysteine levels. CONCLUSIONS:Thus, it may be concluded that hyperhomocysteinemia-induced cardiac hypertrophy is associated with an increase in oxidative stress and density of mast cells in heart. Sodium cromoglycate and ketotifen may have attenuated hyperhomocysteinemia-induced pathological cardiac hypertrophy, possibly by reducing oxidative stress and preventing the degranulation and increase in density of mast cells.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Singh AP,Singh M,Balakumar P

doi

10.1097/FJC.0b013e31817ae60f

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

596-604

issue

eissn

0160-2446

issn

1533-4023

journal_volume

pub_type

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Effect of mast cell stabilizers in hyperhomocysteinemia-induced cardiac hypertrophy in rats.