Folic acid and vitamin B(12) supplementation attenuates isoprenaline-induced myocardial infarction in experimental hyperhomocysteinemic rats

Abstract

Hyperhomocysteinemia (Hhcy) is an independent risk factor for cardiovascular disease. Oxidative stress may contribute to the deleterious effects of homocysteine (Hcy). The aim of the present study is to study the effect of folic acid and Vitamin B(12) supplementation on isoprenaline (ISO)-induced myocardial infarction (MI) in hyperhomocysteinemic rats. Hhcy was induced by daily intake of methionine (1 g kg(-1) body weight) in the drinking water for 4 weeks. MI was then produced by a single subcutaneous injection of ISO (300 mg kg(-1), s.c.). Electrocardiographic parameters, heart rate, ST segment, and blood pressure as well as serum marker enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) were measured. Lipid peroxidation measured as malondialdehyde (MDA) and reduced glutathione (GSH) concentrations in heart tissue were estimated as indices of oxidative stress. Hhcy resulted in significant blood pressure reduction, ST segment elevation and increase in heart rate and serum CK and LDH levels. Cardiac MDA was significantly increased, while GSH was decreased in Hhcy group compared to the normal control group. All the measured parameters were greatly exaggerated in Hhcy rats treated with ISO in comparison with Hhcy rats alone. Administration of folic acid (10 mg kg(-1), orally via gavage) and Vitamin B(12) (500 microg kg(-1), i.m.) concurrently for 4 weeks during the induction of Hhcy markedly reduced the increase in heart rate, ST segment elevation and blood pressure reduction as well as the increase in serum CK and LDH levels. Cardiac MDA content was decreased while cardiac GSH was elevated in the treated group compared to Hhcy + ISO group. Moreover, the severe cardiac histopathological changes observed in Hhcy + ISO group were attenuated by folic acid and Vitamin B(12). These results suggest that Hhcy aggravates MI via oxidative stress mechanisms and that lowering Hcy level with folic acid and Vitamin B(12) can ameliorate the detrimental effects of Hhcy and may reduce the risk of MI.