Dataset Information

Xenobiotic transporters and kidney injury.

ABSTRACT: Renal proximal tubules are targets for toxicity due in part to the expression of transporters that mediate the secretion and reabsorption of xenobiotics. Alterations in transporter expression and/or function can enhance the accumulation of toxicants and sensitize the kidneys to injury. This can be observed when xenobiotic uptake by carrier proteins is increased or efflux of toxicants and their metabolites is reduced. Nephrotoxic chemicals include environmental contaminants (halogenated hydrocarbon solvents, the herbicide paraquat, the fungal toxin ochratoxin, and heavy metals) as well as pharmaceuticals (certain beta-lactam antibiotics, antiviral drugs, and chemotherapeutic drugs). This review explores the mechanisms by which transporters mediate the entry and exit of toxicants from renal tubule cells and influence the degree of kidney injury. Delineating how transport proteins regulate the renal accumulation of toxicants is critical for understanding the likelihood of nephrotoxicity resulting from competition for excretion or genetic polymorphisms that affect transporter function.

SUBMITTER: George B

PROVIDER: S-EPMC5519456 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Xenobiotic transporters and kidney injury.

George Blessy B You Dahea D Joy Melanie S MS Aleksunes Lauren M LM

Advanced drug delivery reviews 20170120

Renal proximal tubules are targets for toxicity due in part to the expression of transporters that mediate the secretion and reabsorption of xenobiotics. Alterations in transporter expression and/or function can enhance the accumulation of toxicants and sensitize the kidneys to injury. This can be observed when xenobiotic uptake by carrier proteins is increased or efflux of toxicants and their metabolites is reduced. Nephrotoxic chemicals include environmental contaminants (halogenated hydrocarb ...[more]

PMID: 28111348

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Project description:Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug resistance-associated proteins (MRP) 1 to 9, breast cancer resistance protein, and ATP-binding cassette subfamily G members 5 and 8, are responsible for the unidirectional export of endogenous and exogenous substances. Other efflux transporters [ATPase copper-transporting beta polypeptide (ATP7B) and ATPase class I type 8B member 1 (ATP8B1) as well as organic solute transporters (OST) alpha and beta] also play major roles in the transport of some endogenous chemicals across biological membranes. This review article provides a comprehensive overview of these transporters (both rodent and human) with regard to tissue distribution, subcellular localization, and substrate preferences. Because uptake and efflux transporters are expressed in multiple cell types, the roles of transporters in a variety of tissues, including the liver, kidneys, intestine, brain, heart, placenta, mammary glands, immune cells, and testes are discussed. Attention is also placed upon a variety of regulatory factors that influence transporter expression and function, including transcriptional activation and post-translational modifications as well as subcellular trafficking. Sex differences, ontogeny, and pharmacological and toxicological regulation of transporters are also addressed. Transporters are important transmembrane proteins that mediate the cellular entry and exit of a wide range of substrates throughout the body and thereby play important roles in human physiology, pharmacology, pathology, and toxicology.

Dataset Information

Xenobiotic transporters and kidney injury.

Publications

Xenobiotic transporters and kidney injury.

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