PMID- 12220963 OWN - NLM STAT- MEDLINE DCOM- 20030314 LR - 20190922 IS - 1043-6618 (Print) IS - 1043-6618 (Linking) VI - 46 IP - 3 DP - 2002 Sep TI - Folic acid and vitamin B(12) supplementation attenuates isoprenaline-induced myocardial infarction in experimental hyperhomocysteinemic rats. PG - 213-19 AB - 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. CI - Copyright 2002 Elsevier Science Ltd. FAU - Hagar, Hanan H AU - Hagar HH AD - Department of Pharmacology, College of Medicine & KHUH, King Saud University, PO Box 2925, Riyadh 11461, Saudi Arabia. hananhager@yahoo.com LA - eng PT - Journal Article PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 4Y8F71G49Q (Malondialdehyde) RN - 935E97BOY8 (Folic Acid) RN - AE28F7PNPL (Methionine) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 2.7.3.2 (Creatine Kinase) RN - GAN16C9B8O (Glutathione) RN - L628TT009W (Isoproterenol) RN - P6YC3EG204 (Vitamin B 12) SB - IM MH - Animals MH - Blood Pressure/drug effects MH - Creatine Kinase/blood/drug effects MH - Folic Acid/*pharmacology/therapeutic use MH - Glutathione/metabolism MH - Heart Rate/drug effects MH - Hemodynamics/drug effects MH - Hyperhomocysteinemia/*prevention & control MH - Isoproterenol/administration & dosage MH - L-Lactate Dehydrogenase/blood/drug effects MH - Lipid Peroxidation/drug effects MH - Male MH - Malondialdehyde/metabolism MH - Methionine/administration & dosage MH - Myocardial Infarction/chemically induced/*prevention & control MH - Myocardium/pathology MH - Oxidative Stress/drug effects MH - Rats MH - Rats, Wistar MH - Vitamin B 12/*pharmacology/therapeutic use EDAT- 2002/09/11 10:00 MHDA- 2003/03/15 04:00 CRDT- 2002/09/11 10:00 PHST- 2002/09/11 10:00 [pubmed] PHST- 2003/03/15 04:00 [medline] PHST- 2002/09/11 10:00 [entrez] AID - S1043661802000956 [pii] AID - 10.1016/s1043-6618(02)00095-6 [doi] PST - ppublish SO - Pharmacol Res. 2002 Sep;46(3):213-19. doi: 10.1016/s1043-6618(02)00095-6.