Folic acid protects against experimental prenatal nicotine-induced cardiac injury by decreasing inflammatory changes, serum TNF and COX-2 expression

Nicotine administration has been shown to increase the risk for cardiovascular diseases and death. The present study was designed to investigate the impact of nicotine administration on serum level tumor necrosis factor and cycloxygenase -2 (COX-2) expression mediated cardiac injury in rat off springs, and the possible protective effect of folic acid. Eighteen pregnant female rats were randomly divided into three groups, six animals each. Control group received the vehicle, nicotine group received a dose of nicotine 0.1 mg/kg body weight, daily with subcutaneous injection from day 3 of gestation until weaning on postnatal day 21. Nicotine treated group received daily oral supplementation with folic acid 200 mg/kg body weight by intragastric tube prior to injection of nicotine. In serum of the pups, levels of tumor necrosis factor (TNF), nitric oxide (NO), total antioxidant capacity (TAC) and malondialdehyde (MDA) were measured. Histopathological studies of cardiac tissues using hematoxylin-eosin (H&E) were carried out. The expression of COX-2 was evaluated using immunohistochemistry. Serum TNF and MDA were significantly increased, while serum NO and TAC were significantly decreased in nicotine group. Moreover, nicotine-exposed rats showed complete lysis of cardiac myocytes, marked cytoplasmic vacuolation of myocytes, muscle fibers show loss of striation and increased COX-2 expression. Concomitant folic acid administration resulted in a significant alleviation of biochemical and structural alteration-induced by nicotine. In conclusion, folic acid has a protective role against nicotine induced cardiac injury by reduction of COX-2 expression, decreasing TNF production and lipid peroxidation mediated cell injury.