Jeffrey C. Sivils, Tiffany M. Ancrum and Lisa J. Bain LOSS of Mrp1 alters detoxification enzyme expression in a tissue- and hormonal-status-specific manner Journal of Applied Toxicology 33
In mice lacking Mrp1, renal phase II and III enzyme expression was significantly changed owing to the loss of androgens, while in the lungs, phase II and phase III enzymes were downregulated in Mrp1−/− mice, irrespective of their hormonal status. Expression in the small intestine was only different between intact and castrated Mrp1−/− mice, and not different in wildtype FVB mice. Enzyme expression patterns correlated to Nrf2 expression. This information will aid in the understanding of how drug uptake, disposition and elimination can be influenced by both hormone status and the presence and magnitude of transporter expression.
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