Influence of Methionine Supplementation on Nicotine Teratogenicity in the Rat

Abstract

Human and animal studies have shown that maternal tobacco smoking during pregnancy adversely affects pre and postnatal growth and increases the risk of fetal mortality. The aim of the present study was to determine the toxicity of nicotine and protective effect of methionine on the toxic effects of nicotine. Pregnant Sprague-Dawley rats were treated from day 9 through 12 of gestation with either nicotine alone (6 mg/kg/day nicotine osmotic minipump or nicotine plus methionine (200 mg/kg) by gavage. Fetuses and embryos were recovered on gestational day-20 or day-12, respectively and were quantitatively and qualitatively assessed for developmental anomalies. Results of the present study showed that nicotine intake during pregnancy had teratogenic effects in the rat. Prenatal growth retardation such as reduced litter weight and crown-rump length, developmental anomalies, and gross external organ malformations were observed in near term fetuses of nicotine treated animals in excess of those in the pair-fed control group. Growth retardation and developmental anomalies were also observed in day-12 embryos of nicotine treated rats. Central nervous system developmental defects, anomalies of the heart, the limbs and the skeleton have also been observed. In the present study, methionine supplementation of the nicotine treated pregnant rats did not protect the rat offspring against the growth retardation and developmental anomalies induced by nicotine in both day-12 embryos and day-20 rat fetuses. Methionine supplementation of animals that were not treated with nicotine did not produce any adverse effects either on the mother, the embryos or the fetuses. The nicotine related growth and developmental abnormalities observed in the present study may not have been directly due to nicotine-induced methionine deficiency or may have been because of presence of an adaptive increase in methionine recycling during methionine deficiency or due to altered methionine metabolism.

Keywords: nicotine, nicotine toxicity, methionine, fetuses, rats