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

Abstract

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 detoxiication 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 cassete 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 endo-and xenobiotics, mainly conjugated with glucuronic acid, glutathione, and sulfate. The small intestine and the liver constitute relevant detoxiication 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 detoxiication processes, and their regulation by xenobiotics, considering in particular its toxicological relevance.

Evaluation of Genetic Polymorphisms of N-acetyltransferase 2 and Relation with Chronic Myeloid Leukemia

“…resistance-associated proteins (MRPs) (Wu and Lin, 2019;Arana et al, 2016). Acetylation is a critical processes of xenobiotic metabolism and involves catalysis by acetyl CoA-dependent aryl amine N-acetyltransferase (NAT) enzymes.…”

The Reduction of the Combined Effects of Aflatoxin and Ochratoxin A in Piglet Livers and Kidneys by Dietary Antioxidants

“…In pigs, such transporters involved in the elimination of mycotoxins' metabolites conjugated with glucuronic acid, reduced glutathione and sulfate are represented by members of transporter family located in the basement membrane of polarized cells, such as MRP2, MRP4, Bcrp, Oat and Oct [19,[23][24][25][26][27][28].…”