EFFECTS OF BISPHENOL A AND NICOTINE ON CYTOCHROME P450S IN BRAIN AND LIVER OF PREGNANT RATS

Abstract

Bisphenol A (BPA), a widely used chemical, is associated with endocrine disruption through its interactions with the aryl hydrocarbon receptor (AhR). BPA crosses into the human body mostly through migration from plastic packaging into the daily diet. AhR regulates the expression of drug-metabolizing enzymes (DMEs), including numerous CYP450s, and mediates xenobiotic reactions. This study aims at examining how the expression of CYP450s expression is affected, in the brain and liver of pregnant rats, by exposure to BPA and nicotine. Pregnant female Sprague-Dawley dams were exposed to increasing doses of BPA; 0 (control), 50, 500, and 5000 g/kg/day , or in combination with nicotine; 3000 µg/kg/day, through drinking water. Brain and liver tissues were isolated after 2 weeks of exposure, and western blotting was used to assess the expression of selected protein targets. The results showed that BPA exposure decreased the expression levels of CYP1A1 and CYP1B1 in the brain (by 55% and 79% respectively). It also decreased CYP2E1 levels in the brain (by 42%), but increased its levels in the liver (by 126%). Moreover, BPA exposure decreased levels of CYP19A1 and ARNT in the liver (by 51% and 44% respectively), and decreased those of AhRR (AhR repressor) in the brain (by 28%). On the other hand, nicotine treatment exhibited an inhibitory effect with CYP1A1, CYP1B1, and AhRR in the brain (by 67%, 78%, and 13% respectively), whereas, it inhibited CYP1A1, CYP19A1, and ARNT (AhR Nuclear Translocator) in the liver (47%, 54%, and 63% respectively). In conclusion, adult brain and liver tissues showed BPA sensitivity, which disrupts CYP450s expression, and is modulated by nicotine. The observed effects could be mediated by AhR-ARNT-dependent or independent pathways, which need to be investigated further.