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We are daily exposed to a large number of pharmacological drugs, environmental pollutants, and natural toxins, which represent a potential toxic insult. The organism possesses a sophisticated system of detoxification particularly expressed in the liver, intestine, and kidney. This system consists of intracellular biotransformation enzymes that convert the toxins into more hydrophilic derivatives followed by their elimination through membrane transporters. Multidrug resistance-associated protein 2 (MRP2, ABCC2) is an important member of the ATP-binding cassette (ABC) superfamily of transporters localized at the apical membrane of polarized cells, such as hepatocytes, enterocytes, and renal tubular cells. MRP2 is proposed as a major actor in the elimination of endoand xenobiotics, mainly conjugated with glucuronic acid, glutathione, and sulfate. The small intestine and the liver constitute relevant detoxification organs expressing MRP2 and therefore preventing absorption and promoting the hepatobiliary clearance of xenobiotics. MRP2 expression and/or function can be modulated by therapeutic drugs, herbal products, dietary compounds, and environmental pollutants. Consequently, MRP2 modulation could cause changes in tissue exposure, with potential toxicological and pharmacological consequences. This chapter reviews the information available on the role of hepatic and intestinal MRP2 in detoxification processes, and their regulation by xenobiotics, considering in particular its toxicological relevance.

Hepatic and Intestinal Multidrug Resistance-Associated Protein 2: Transcriptional and Post-transcriptional Regulation by Xenobiotics