Maternal nicotine exposure and antioxidant capacity in the brains of offspring

Nicotine is an emerging teratogen and a potent oxidant as it readily crosses the placenta and compromises the development of critical neural pathways in the developing brain, which is thought to be the cause of many of the adverse neurobehavioral outcomes in the offspring of women who smoke during pregnancy. We hypothesize that the oxidative stress to the brains caused by prenatal nicotine exposure (PNE) is linked to reduced translation of the antioxidant enzymes catalase (Cat), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Timed pregnant C57B1/6 mice were exposed to 200mcg/ml nicotine base and a 2% saccharin solution (PNE group) or 2% saccharin placebo (CTR group) via the Drinking in the Dark protocol throughout gestation and until weaning. Quantitative real-time RT-PCR, Western blot, and enzyme activity analyses were performed on brain samples from female (CTR n=6, PNE n=13) and male pups (CTR n=11, PNE n=14) collected at 6 months of age. Student t-test or Mann-Whitney test were used for statistical analysis as appropriate (significance: P < 0.05). Cat mRNA levels were significantly increased in PNE males when compared to CTR group (P=0.003). An increased Cat activity was found in both PNE males and females when compared to CTR animals (P=0.002 and P=0.04, respectively). SOD protein levels were significantly higher PNE females versus placebo females (P=0.03). GPx mRNA was significantly lower in PNE males as compared to CTRs (P=0.04). The protein levels of GPx 92kDa subunit was increased while 23kDa subunit was decreased in PNE males as compared to CTR groups (P=0.02 and P=0.03, respectively). No other differences between the PNE and CTR groups were found. Prenatal and early postnatal exposure to PNE has varying effects on gene expression, protein levels and activity of the antioxidant enzymes Cat, SOD, and GPx in rodent offspring. Contrary to our hypothesis, the most effects were upregulated. It is possible that PNE due to maternal intake results in augmentation of antioxidant enzyme protective function in the offspring. Further studies are needed to determine the clinical consequences of these effects.