Effect of mast cell stabilizers in hyperhomocysteinemia-induced cardiac hypertrophy in rats.
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.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Amrit Pal
AP
Singh
Manjeet
M
Singh
Pitchai
P
Balakumar
D000818:Animals; D001794:Blood Pressure; D003094:Collagen / Q000096:biosynthesis; D004205:Cromolyn Sodium / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D020138:Hyperhomocysteinemia / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D008715:Methionine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D003094:Collagen; D008715:Methionine; D004205:Cromolyn Sodium; D007665:Ketotifen