Nonylphenol (NP) is a degradation product of the nonylphenol ethoxylates. The United States Geological Survey showed that NP is one of the top 7 most commonly found organic environmental contaminants in water, and when present, is usually the contaminant found at the highest concentration. Furthermore, NP is the only chemical found more than 70% of the time above suggested limits in waste sludges. The reason NP is ubiquitous throughout the United States and Europe is because it is a high use chemical resistant to biodegradation. This makes NP a toxicant of concern. NP's toxicant-toxicant and drug-toxicant interactions are unknown. Adverse drug reactions are common, and the cause of most is unknown. Exposure to environmental chemicals such as NP may increase adverse drug reactions. NP activates the pregnane X-receptor (PXR) and our data suggests it activates the constitutive androstane receptor (CAR). These nuclear receptors are important in regulating the expression of Cyp2b and CypSa; two P450s often involved in adverse drug reactions. Furthermore, our data indicates that NP causes gender specific P450 induction and therefore exposure to NP may cause distinct pharmacological and toxicological effects in males compared to females. In summary, recognition of the occupational and environmental hazards that induce P450s and increase potential drug-drug interactions can lead to alternative pharmacological strategies and ultimately save lives. The goal of this study is to (1) determine whether NP induces P450s in a gender-specific manner, (2) test whether NP induces the drug-metabolizing P450s (CYPs) by activating CAR, and (3) test the pharmacological significance of P450 induction. ? ? ?
| Hernandez, J P; Mota, L C; Huang, W et al. (2009) Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR). Toxicology 256:53-64 |
| Hernandez, J P; Mota, L C; Baldwin, W S (2009) Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation. Curr Pharmacogenomics Person Med 7:81-105 |
| Hernandez, Juan P; Huang, Wendong; Chapman, Laura M et al. (2007) The environmental estrogen, nonylphenol, activates the constitutive androstane receptor. Toxicol Sci 98:416-26 |
| Hernandez, Juan P; Chapman, Laura M; Kretschmer, Xiomara C et al. (2006) Gender-specific induction of cytochrome P450s in nonylphenol-treated FVB/NJ mice. Toxicol Appl Pharmacol 216:186-96 |
