肾脏有机阳离子转运体2在急性肾损伤中病理生理调控的研究进展
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摘要
有机阳离子转运体2(organic cation transporter 2,OCT2)是溶质转运体(solute carriers,SLC)超家族中SLC22A家族的重要成员之一。肾小管上皮细胞基底膜侧表达的OCT2在维持机体内环境平衡方面起着重要作用,是肾脏主动分泌众多内、外源性有机阳离子型化合物(包括环境毒素、药物以及内源性代谢产物等)的主要转运体。在急性肾损伤(acute kidney injury,AKI)期间,OCT2功能与表达的改变对其底物的清除具有巨大的影响,可导致药物的药代动力学过程发生改变,从而影响药物的安全性和有效性。现就OCT2的结构与分布、生理作用与调控机制以及在各种因素诱导的AKI中的功能与表达变化和病理生理调控等方面进行综述,旨在为临床合理用药提供参考。
Orangic cation transporter 2(OCT2) is an important member of superfamily of solute carriers 22 A(SLC22 A). As a major transporter involved in both endogenous and exogenous active secretion in the basolateral of renal tubular epithelial, OCT2 can transport drugs, toxins and endogenous by-products in kidney, and therefore, plays an important role in maintaining the homeostasis of internal environment. Under the circumstance of acute kidney injury(AKI), the functional and expressional variations of renal OCT2 have a huge impact on systemic clearance of substrate drugs, thereby affecting the safety and efficacy of the drug. This review highlights the structure and distribution of OCT2, its physiological effects and regulation mechanism, as well as its function and expression changes and pathophysiological regulation in a variety of factors inducing AKI, aiming to provide theoretical basis for the rational use of drugs.
Orangic cation transporter 2(OCT2) is an important member of superfamily of solute carriers 22 A(SLC22 A). As a major transporter involved in both endogenous and exogenous active secretion in the basolateral of renal tubular epithelial, OCT2 can transport drugs, toxins and endogenous by-products in kidney, and therefore, plays an important role in maintaining the homeostasis of internal environment. Under the circumstance of acute kidney injury(AKI), the functional and expressional variations of renal OCT2 have a huge impact on systemic clearance of substrate drugs, thereby affecting the safety and efficacy of the drug. This review highlights the structure and distribution of OCT2, its physiological effects and regulation mechanism, as well as its function and expression changes and pathophysiological regulation in a variety of factors inducing AKI, aiming to provide theoretical basis for the rational use of drugs.
引文
[1]Yin J,Wang J.Renal drug transporters and their significance in drug-drug interactions.Acta Pharm Sin B,2016,6:363-73
[2]Li LP,Song FF,Weng YY,et al.Role of OCT2 and MATE1 in renal disposition and toxicity of nitidine chloride.Br J Pharmacol,2016,173:2543-54
[3]Koepsell H.The SLC22 family with transporters of organic cations,anions and zwitterions.Mol Aspects Med,2013,34:413-35
[4]Robertson EE,Rankin GO.Human renal organic anion transporters:characteristics and contributions to drug and drug metabolite excretion.Pharmacol Ther,2006,109:399-412
[5]Yin G,Chen X.Diagnostic criteria of acute kidney injury.Med J West China,2013,25:1916-8
[6]Min HE,Sang XH.Research progress in blood purification treatment for acute kidney injury.Med Recapitul,2013,52:933-8
[7]Shanley PF,Rosen MD,Brezis M,et al.Topography of focal proximal tubular necrosis after ischemia with reflow in the rat kidney.Am J Pathol,1986,122:462-8
[8]Okuda M,Saito H,Urakami Y,et al.c DNA cloning and functional expression of a novel rat kidney organic cation transporter,OCT2.Biochem Biophys Res Commun,1996,224:500-7
[9]Grundemann D,Gorboulev V,Gambaryan S,et al.Drug excretion mediated by a new prototype of polyspecific transporter.Nature,1994,372:549-52
[10]Saito H.Pathophysiological regulation of renal SLC22A organicion transporters in acute kidney injury:pharmacological and toxicological implications.Pharmacol Ther,2010,125:79-91
[11]Urakami Y,Okuda M,Masuda S,et al.Functional characteristics and membrane localization of rat multispecific organic cation transporters,OCT1 and OCT2,mediating tubular secretion of cationic drugs.J Pharmacol Exp Ther,1998,287:800-5
[12]Koepsell H,Gorboulev V,Arndt P.Molecular pharmacology of organic cation transporters in kidney.J Membr Biol,1999,167:103-17
[13]Okuda M,Urakami Y,Saito H,et al.Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes.Biochim Biophys Acta,1999,1417:224-31
[14]Karbach U,Kricke J,Meyer-Wentrup F,et al.Localization of organic cation transporters OCT1 and OCT2 in rat kidney.Am J Physiol Renal Physiol,2000,279:F679-87
[15]Sweet DH,Miller DS,Pritchard JB.Basolateral localization of organic cation transporter 2 in intact renal proximal tubules.Am J Physiol Renal Physiol,2000,279:F826-34
[16]Busch AE,Karbach U,Miska D,et al.Human neurons express the polyspecific cation transporter h OCT2,which translocates monoamine neurotransmitters,amantadine,and memantine.Mol Pharmacol,1998,54:342-52
[17]Inui KI,Okuda M.Cellular and molecular mechanisms of renal tubular secretion of organic anions and cations.Clin Exp Nephrol,1998,2:100-8
[18]Chen DD,Xiao J,Zhou HH.Recent advancement in human organic cation transporter 2 and its genetic variants.Med Recapitul,2008,14:1302-4
[19]Urakami Y,Nakamura N,Takahashi K,et al.Gender differences in expression of organic cation transporter OCT2 in rat kidney.FEBS Lett,1999,461:339-42
[20]Urakami Y,Okuda M,Saito H,et al.Hormonal regulation of organic cation transporter OCT2 expression in rat kidney.FEBS Lett,2000,473:173-6
[21]Shu Y,Bello CL,Mangravite LM,et al.Functional characteristics and steroid hormone-mediated regulation of an organic cation transporter in Madin-Darby canine kidney cells.J Pharmacol Exp Ther,2001,299:392-8
[22]Asaka J,Terada T,Ogasawara K,et al.Characterization of the basal promoter element of human organic cation transporter 2 gene.J Pharmacol Exp Ther,2007,321:684-9
[23]Asaka J,Terada T,Okuda M,et al.Androgen receptor is responsible for rat organic cation transporter 2 gene regulation but not for r OCT1 and r OCT3.Pharm Res,2006,23:697-704
[24]Cetinkaya I,Ciarimboli G,Yalcinkaya G,et al.Regulation of human organic cation transporter h OCT2 by PKA,PI3K,and calmodulin-dependent kinases.Am J Physiol Renal Physiol,2003,284:F293-302
[25]Dresser MJ,Xiao G,Leabman MK,et al.Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter(h OCT2).Pharm Res,2002,19:1244-7
[26]Soodvilai S,Chatsudthipong A,Chatsudthipong V.Role of MAPK and PKA in regulation of rb OCT2-mediated renal organic cation transport.Am J Physiol Renal Physiol,2007,293:F21-7
[27]Aoki M,Terada T,Kajiwara M,et al.Kidney-specific expression of human organic cation transporter 2(OCT2/SLC22A2)is regulated by DNA methylation.Am J Physiol Renal Physiol,2008,295:F165-70
[28]Malek M,Nematbakhsh M.Renal ischemia/reperfusion injury:from pathophysiology to treatment.J Renal Inj Prev,2015,4:20-7
[29]Rodriguez F,Bonacasa B,Fenoy FJ,et al.Reactive oxygen and nitrogen species in the renal ischemia/reperfusion injury.Curr Pharm Des,2013,19:2776-94
[30]Schrier RW,Wang W,Poole B,et al.Acute renal failure:definitions,diagnosis,pathogenesis,and therapy.J Clin Invest,2004,114:5-14
[31]Molitoris BA,Dahl R,Geerdes A.Cytoskeleton disruption and apical redistribution of proximal tubule Na+-K+-ATPase during ischemia.Am J Physiol,1992,263:F488-95
[32]Inotsume N,Nishimura M,Fujiyama S,et al.Pharmacokinetics of famotidine in elderly patients with and without renal insufficiency and in healthy young volunteers.Eur J Clin Pharmacol,1989,36:517-20
[33]Matsuzaki T,Morisaki T,Sugimoto W,et al.Altered pharmacokinetics of cationic drugs caused by downregulation of renal rat organic cation transporter 2(Slc22a2)and rat multidrug and toxin extrusion 1(Slc47a1)in ischemia/reperfusion-induced acute kidney injury.Drug Metab Dispos,2008,36:649-54
[34]Tahara H,Kusuhara H,Endou H,et al.A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters.J Pharmacol Exp Ther,2005,315:337-45
[35]Ji L,Masuda S,Saito H,et al.Down-regulation of rat organic cation transporter r OCT2 by 5/6 nephrectomy.Kidney Int,2002,62:514-24
[36]Park KM,Kim JI,Ahn Y,et al.Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury.J Biol Chem,2004,279:52282-92
[37]Shim WS,Park JH,Ahn SJ,et al.Testosteron eindependent down-regulation of Oct2 in the kidney medulla from a uranyl nitrate-induced rat model of acute renal failure:effects on distribution of a model organic cation,tetraethylammonium.J Pharm Sci,2009,98:739-47
[38]Masubuchi Y,Kawasaki M,Horie T.Down-regulation of hepatic cytochrome P450 enzymes associated with cisplatin-induced acute renal failure in male rats.Arch Toxicol,2006,80:347-53
[39]Shord SS,Thompson DM,Krempl GA,et al.Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients with head and neck cancer.Anticancer Drugs,2006,17:207-15
[40]Ciarimboli G,Ludwig T,Lang D,et al.Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2.Am J Pathol,2005,167:1477-84
[41]Yonezawa A,Masuda S,Nishihara K,et al.Association between tubular toxicity of cisplatin and expression of organic cation transporter r OCT2(Slc22a2)in the rat.Biochem Pharmacol,2005,70:1823-31
[42]Manohar S,Leung N.Cisplatin nephrotoxicity:a review of the literature.J Nephrol,2018,31:15-25
[43]Aleksunes LM,Augustine LM,Scheffer GL,et al.Renal xenobiotic transporters are differentially expressed in mice following cisplatin treatment.Toxicology,2008,250:82-8
[44]Thomas J,Wang L,Clark RE,et al.Active transport of imatinib into and out of cells:implications for drug resistance.Blood,2004,104:3739-45
[45]Wang L,Giannoudis A,Lane S,et al.Expression of the uptake drug transporter h OCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia.Clin Pharmacol Ther,2008,83:258-64
[46]Tanihara Y,Masuda S,Katsura T,et al.Protective effect of concomitant administration of imatinib on cisplatininduced nephrotoxicity focusing on renal organic cation transporter OCT2.Biochem Pharmacol,2009,78:1263-71
[47]Schilsky RL,Barlock A,Ozols RF.Persistent hypomagnesemia following cisplatin chemotherapy for testicular cancer.Cancer Treat Rep,1982,66:1767-9
[48]Lajer H,Daugaard G.Cisplatin and hypomagnesemia.Cancer Treat Rev,1999,25:47-58
[49]Mavichak V,Wong NL,Quamme GA,et al.Studies on the pathogenesis of cisplatin-induced hypomagnesemia in rats.Kidney Int,1985,28:914-21
[50]Yao X,Panichpisal K,Kurtzman N,et al.Cisplatin nephrotoxicity:a review.Am J Med Sci,2007,334:115-24
[51]Yokoo K,Murakami R,Matsuzaki T,et al.Enhanced renal accumulation of cisplatin via renal organic cation transporter deteriorates acute kidney injury in hypomagnesemic rats.Clin Exp Nephrol,2009,13:578-84
[52]Gobe G,Crane D.Mitochondria,reactive oxygen species and cadmium toxicity in the kidney.Toxicol Lett,2010,198:49-55
[53]Dorian C,Gattone VH 2nd,Klaasen CD.Renal cadmium deposition and injury as a result of accumulation of cadmium-metallothionein(Cd MT)by the proximal convoluted tubules--A light microscopic autoradiography study with 109Cd MT.Toxicol Appl Pharmacol,1992,114:173-81
[54]Suzuki CA,Cherian MG.Effects of cadmiummetallothionein on renal organic ion transport and lipid peroxidation in rats.J Biochem Toxicol,1988,3:11-20
[55]Nikiforov AA,Ostretsova IB.Stimulation of weak organic acid uptake in rat renal tubules by cadmium and nystatin.Biochem Pharmacol,1994,47:815-20
[56]Hohage H,Mehrens T,Mergelsberg U,et al.Effects of extracellular cadmium on renal basolateral organic anion transport.Toxicol Lett,1998,98:189-94
[57]Soodvilai S,Nantavishit J,Muanprasat C,et al.Renal organic cation transporters mediated cadmium-induced nephrotoxicity.Toxicol Lett,2011,204:38-42
[58]Lee HY,Kim KR,Woo JS,et al.Transport of organic compounds in renal plasma membrane vesicles of cadmium intoxicated rats.Kidney Int,1990,37:727-35
[59]Kim KR,Kim GC,Choi JS,et al.Renal transport systems for organic anions and cations in cadmium-exposed rats.Toxicol Appl Pharmacol,1998,149:144-9
[60]Ljubojevi?M,Breljak D,Herak-Kramberger CM,et al.Expression of basolateral organic anion and cation transporters in experimental cadmium nephrotoxicity in rat kidney.Arch Toxicol,2016,90:525-41
[2]Li LP,Song FF,Weng YY,et al.Role of OCT2 and MATE1 in renal disposition and toxicity of nitidine chloride.Br J Pharmacol,2016,173:2543-54
[3]Koepsell H.The SLC22 family with transporters of organic cations,anions and zwitterions.Mol Aspects Med,2013,34:413-35
[4]Robertson EE,Rankin GO.Human renal organic anion transporters:characteristics and contributions to drug and drug metabolite excretion.Pharmacol Ther,2006,109:399-412
[5]Yin G,Chen X.Diagnostic criteria of acute kidney injury.Med J West China,2013,25:1916-8
[6]Min HE,Sang XH.Research progress in blood purification treatment for acute kidney injury.Med Recapitul,2013,52:933-8
[7]Shanley PF,Rosen MD,Brezis M,et al.Topography of focal proximal tubular necrosis after ischemia with reflow in the rat kidney.Am J Pathol,1986,122:462-8
[8]Okuda M,Saito H,Urakami Y,et al.c DNA cloning and functional expression of a novel rat kidney organic cation transporter,OCT2.Biochem Biophys Res Commun,1996,224:500-7
[9]Grundemann D,Gorboulev V,Gambaryan S,et al.Drug excretion mediated by a new prototype of polyspecific transporter.Nature,1994,372:549-52
[10]Saito H.Pathophysiological regulation of renal SLC22A organicion transporters in acute kidney injury:pharmacological and toxicological implications.Pharmacol Ther,2010,125:79-91
[11]Urakami Y,Okuda M,Masuda S,et al.Functional characteristics and membrane localization of rat multispecific organic cation transporters,OCT1 and OCT2,mediating tubular secretion of cationic drugs.J Pharmacol Exp Ther,1998,287:800-5
[12]Koepsell H,Gorboulev V,Arndt P.Molecular pharmacology of organic cation transporters in kidney.J Membr Biol,1999,167:103-17
[13]Okuda M,Urakami Y,Saito H,et al.Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes.Biochim Biophys Acta,1999,1417:224-31
[14]Karbach U,Kricke J,Meyer-Wentrup F,et al.Localization of organic cation transporters OCT1 and OCT2 in rat kidney.Am J Physiol Renal Physiol,2000,279:F679-87
[15]Sweet DH,Miller DS,Pritchard JB.Basolateral localization of organic cation transporter 2 in intact renal proximal tubules.Am J Physiol Renal Physiol,2000,279:F826-34
[16]Busch AE,Karbach U,Miska D,et al.Human neurons express the polyspecific cation transporter h OCT2,which translocates monoamine neurotransmitters,amantadine,and memantine.Mol Pharmacol,1998,54:342-52
[17]Inui KI,Okuda M.Cellular and molecular mechanisms of renal tubular secretion of organic anions and cations.Clin Exp Nephrol,1998,2:100-8
[18]Chen DD,Xiao J,Zhou HH.Recent advancement in human organic cation transporter 2 and its genetic variants.Med Recapitul,2008,14:1302-4
[19]Urakami Y,Nakamura N,Takahashi K,et al.Gender differences in expression of organic cation transporter OCT2 in rat kidney.FEBS Lett,1999,461:339-42
[20]Urakami Y,Okuda M,Saito H,et al.Hormonal regulation of organic cation transporter OCT2 expression in rat kidney.FEBS Lett,2000,473:173-6
[21]Shu Y,Bello CL,Mangravite LM,et al.Functional characteristics and steroid hormone-mediated regulation of an organic cation transporter in Madin-Darby canine kidney cells.J Pharmacol Exp Ther,2001,299:392-8
[22]Asaka J,Terada T,Ogasawara K,et al.Characterization of the basal promoter element of human organic cation transporter 2 gene.J Pharmacol Exp Ther,2007,321:684-9
[23]Asaka J,Terada T,Okuda M,et al.Androgen receptor is responsible for rat organic cation transporter 2 gene regulation but not for r OCT1 and r OCT3.Pharm Res,2006,23:697-704
[24]Cetinkaya I,Ciarimboli G,Yalcinkaya G,et al.Regulation of human organic cation transporter h OCT2 by PKA,PI3K,and calmodulin-dependent kinases.Am J Physiol Renal Physiol,2003,284:F293-302
[25]Dresser MJ,Xiao G,Leabman MK,et al.Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter(h OCT2).Pharm Res,2002,19:1244-7
[26]Soodvilai S,Chatsudthipong A,Chatsudthipong V.Role of MAPK and PKA in regulation of rb OCT2-mediated renal organic cation transport.Am J Physiol Renal Physiol,2007,293:F21-7
[27]Aoki M,Terada T,Kajiwara M,et al.Kidney-specific expression of human organic cation transporter 2(OCT2/SLC22A2)is regulated by DNA methylation.Am J Physiol Renal Physiol,2008,295:F165-70
[28]Malek M,Nematbakhsh M.Renal ischemia/reperfusion injury:from pathophysiology to treatment.J Renal Inj Prev,2015,4:20-7
[29]Rodriguez F,Bonacasa B,Fenoy FJ,et al.Reactive oxygen and nitrogen species in the renal ischemia/reperfusion injury.Curr Pharm Des,2013,19:2776-94
[30]Schrier RW,Wang W,Poole B,et al.Acute renal failure:definitions,diagnosis,pathogenesis,and therapy.J Clin Invest,2004,114:5-14
[31]Molitoris BA,Dahl R,Geerdes A.Cytoskeleton disruption and apical redistribution of proximal tubule Na+-K+-ATPase during ischemia.Am J Physiol,1992,263:F488-95
[32]Inotsume N,Nishimura M,Fujiyama S,et al.Pharmacokinetics of famotidine in elderly patients with and without renal insufficiency and in healthy young volunteers.Eur J Clin Pharmacol,1989,36:517-20
[33]Matsuzaki T,Morisaki T,Sugimoto W,et al.Altered pharmacokinetics of cationic drugs caused by downregulation of renal rat organic cation transporter 2(Slc22a2)and rat multidrug and toxin extrusion 1(Slc47a1)in ischemia/reperfusion-induced acute kidney injury.Drug Metab Dispos,2008,36:649-54
[34]Tahara H,Kusuhara H,Endou H,et al.A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters.J Pharmacol Exp Ther,2005,315:337-45
[35]Ji L,Masuda S,Saito H,et al.Down-regulation of rat organic cation transporter r OCT2 by 5/6 nephrectomy.Kidney Int,2002,62:514-24
[36]Park KM,Kim JI,Ahn Y,et al.Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury.J Biol Chem,2004,279:52282-92
[37]Shim WS,Park JH,Ahn SJ,et al.Testosteron eindependent down-regulation of Oct2 in the kidney medulla from a uranyl nitrate-induced rat model of acute renal failure:effects on distribution of a model organic cation,tetraethylammonium.J Pharm Sci,2009,98:739-47
[38]Masubuchi Y,Kawasaki M,Horie T.Down-regulation of hepatic cytochrome P450 enzymes associated with cisplatin-induced acute renal failure in male rats.Arch Toxicol,2006,80:347-53
[39]Shord SS,Thompson DM,Krempl GA,et al.Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients with head and neck cancer.Anticancer Drugs,2006,17:207-15
[40]Ciarimboli G,Ludwig T,Lang D,et al.Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2.Am J Pathol,2005,167:1477-84
[41]Yonezawa A,Masuda S,Nishihara K,et al.Association between tubular toxicity of cisplatin and expression of organic cation transporter r OCT2(Slc22a2)in the rat.Biochem Pharmacol,2005,70:1823-31
[42]Manohar S,Leung N.Cisplatin nephrotoxicity:a review of the literature.J Nephrol,2018,31:15-25
[43]Aleksunes LM,Augustine LM,Scheffer GL,et al.Renal xenobiotic transporters are differentially expressed in mice following cisplatin treatment.Toxicology,2008,250:82-8
[44]Thomas J,Wang L,Clark RE,et al.Active transport of imatinib into and out of cells:implications for drug resistance.Blood,2004,104:3739-45
[45]Wang L,Giannoudis A,Lane S,et al.Expression of the uptake drug transporter h OCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia.Clin Pharmacol Ther,2008,83:258-64
[46]Tanihara Y,Masuda S,Katsura T,et al.Protective effect of concomitant administration of imatinib on cisplatininduced nephrotoxicity focusing on renal organic cation transporter OCT2.Biochem Pharmacol,2009,78:1263-71
[47]Schilsky RL,Barlock A,Ozols RF.Persistent hypomagnesemia following cisplatin chemotherapy for testicular cancer.Cancer Treat Rep,1982,66:1767-9
[48]Lajer H,Daugaard G.Cisplatin and hypomagnesemia.Cancer Treat Rev,1999,25:47-58
[49]Mavichak V,Wong NL,Quamme GA,et al.Studies on the pathogenesis of cisplatin-induced hypomagnesemia in rats.Kidney Int,1985,28:914-21
[50]Yao X,Panichpisal K,Kurtzman N,et al.Cisplatin nephrotoxicity:a review.Am J Med Sci,2007,334:115-24
[51]Yokoo K,Murakami R,Matsuzaki T,et al.Enhanced renal accumulation of cisplatin via renal organic cation transporter deteriorates acute kidney injury in hypomagnesemic rats.Clin Exp Nephrol,2009,13:578-84
[52]Gobe G,Crane D.Mitochondria,reactive oxygen species and cadmium toxicity in the kidney.Toxicol Lett,2010,198:49-55
[53]Dorian C,Gattone VH 2nd,Klaasen CD.Renal cadmium deposition and injury as a result of accumulation of cadmium-metallothionein(Cd MT)by the proximal convoluted tubules--A light microscopic autoradiography study with 109Cd MT.Toxicol Appl Pharmacol,1992,114:173-81
[54]Suzuki CA,Cherian MG.Effects of cadmiummetallothionein on renal organic ion transport and lipid peroxidation in rats.J Biochem Toxicol,1988,3:11-20
[55]Nikiforov AA,Ostretsova IB.Stimulation of weak organic acid uptake in rat renal tubules by cadmium and nystatin.Biochem Pharmacol,1994,47:815-20
[56]Hohage H,Mehrens T,Mergelsberg U,et al.Effects of extracellular cadmium on renal basolateral organic anion transport.Toxicol Lett,1998,98:189-94
[57]Soodvilai S,Nantavishit J,Muanprasat C,et al.Renal organic cation transporters mediated cadmium-induced nephrotoxicity.Toxicol Lett,2011,204:38-42
[58]Lee HY,Kim KR,Woo JS,et al.Transport of organic compounds in renal plasma membrane vesicles of cadmium intoxicated rats.Kidney Int,1990,37:727-35
[59]Kim KR,Kim GC,Choi JS,et al.Renal transport systems for organic anions and cations in cadmium-exposed rats.Toxicol Appl Pharmacol,1998,149:144-9
[60]Ljubojevi?M,Breljak D,Herak-Kramberger CM,et al.Expression of basolateral organic anion and cation transporters in experimental cadmium nephrotoxicity in rat kidney.Arch Toxicol,2016,90:525-41