The role of folic acid against fetal toxicity induced by aluminium chloride and the response of the brain endogenous antioxidants in pregnant rats and their fetuses.

Abstract

The present study was performed to assess the effectiveness of folic acid (folate) against aluminium - chloride - induced fetal developmental toxicity and the response of cerebral antioxidant enzymes activities in pregnant rats and their fetuses. Pregnant rats were divided into four groups : (1) control (2) rats orally administered AlCl3 at 345 mg/kg b.wt./day (3) rats orally administered folic acid at 20 mg/kg b.wt./day (4) rats administered both folate and AlCl3 at the mentioned dosages . Rats were treated orally with AlCl3 and folate either alone or in combination from the7th to the19th day of gestation. Results obtained showed that AlCl3 caused a significant reduction in maternal body weight gain , fetal body weight, fetal brain weight, placental weight and an increase in dams mortality rate, number of abortions ,number of resorbed fetuses, and skeletal anomalies . Folate alone showed normal ranges in all the previous parameters as those of the control. Folate concurrently with aluminium chloride revealed significant protection for placental weights and fetal skeletal systems. Aluminium chloride alone exhibited an insignificant increment in the activity of brain lactate dehydrogenase (LDH) , significant elevations in the activities of antioxidant enzymes : Glutathione reduced (GSH), Glutathione –S- transferase (GST), Glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation. However, the activities of cholinesterase and catalase showed insignificant reductions comparable to control and folate groups in the brain of both mothers and fetuses. Combined treatment of AlCl3 and folate showed significant protection in the activities of the antioxidant enzymes GPX , SOD and catalase and lipid peroxidation content in brains of mothers and also with fetuses without change in catalase activity and the other antioxidant enzymes. These results suggested that, aluminium chloride has pro-oxidant effect through increment formation of reactive oxygen species (ROS) and lipid peroxidation. The elevation of antioxidant enzyme activities reflects an adaptive response against oxidative stress induced by aluminium chloride. The present study concluded that high oral dose of AlCl3 (1/10 LD50) can induce signs of systemic intoxication and developmental delay in fetuses. Folic acid at 20 mg/kg body wt., which is equivalent to the therapeutic dose, has a limited protective effect against pro-oxidant effect of aluminium in brain of pregnant rats and fetuses and also with the developmental toxicity induced by aluminium chloride.