Transporters and Toxicity: Insights From the International Transporter Consortium Workshop 4.
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
31
03
2022
accepted:
30
04
2022
pubmed:
14
5
2022
medline:
24
8
2022
entrez:
13
5
2022
Statut:
ppublish
Résumé
Over the last decade, significant progress been made in elucidating the role of membrane transporters in altering drug disposition, with important toxicological consequences due to changes in localized concentrations of compounds. The topic of "Transporters and Toxicity" was recently highlighted as a scientific session at the International Transporter Consortium (ITC) Workshop 4 in 2021. The current white paper is not intended to be an extensive review on the topic of transporters and toxicity but an opportunity to highlight aspects of the role of transporters in various toxicities with clinically relevant implications as covered during the session. This includes a review of the role of solute carrier transporters in anticancer drug-induced organ injury, transporters as key players in organ barrier function, and the role of transporters in metal/metalloid toxicity.
Substances chimiques
Membrane Transport Proteins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
527-539Informations de copyright
© 2022 The Authors. Clinical Pharmacology & Therapeutics © 2022 American Society for Clinical Pharmacology and Therapeutics.
Références
International Transporter Consortium, et al. Membrane transporters in drug development. Nat. Rev. Drug Discov. 9, 215-236 (2010).
Hillgren, K.M. et al. Emerging transporters of clinical importance: an update from the International Transporter Consortium. Clin. Pharmacol. Ther. 94, 52-63 (2013).
Tweedie, D. et al. Transporter studies in drug development: experience to date and follow-up on decision trees from the International Transporter Consortium. Clin. Pharmacol. Ther. 94, 113-125 (2013).
Zamek-Gliszczynski, M.J. et al. Transporters in drug development: 2018 ITC recommendations for transporters of emerging clinical importance. Clin. Pharmacol. Ther. 104, 890-899 (2018).
Kenna, J.G. et al. Can bile salt export pump inhibition testing in drug discovery and development reduce liver injury risk? An international transporter consortium perspective. Clin. Pharmacol. Ther. 104, 916-932 (2018).
Lin, L., Yee, S.W., Kim, R.B. & Giacomini, K.M. SLC transporters as therapeutic targets: emerging opportunities. Nat. Rev. Drug Discov. 14, 543-560 (2015).
Schuetz, J.D., Swaan, P.W. & Tweedie, D.J. The role of transporters in toxicity and disease. Drug Metab. Dispos. 42, 541-545 (2014).
Pan, G. Roles of hepatic drug transporters in drug disposition and liver toxicity. Adv. Exp. Med. Biol. 1141, 293-340 (2019).
Hu, S. & Sprowl, J.A. Strategies to reduce solute carrier-mediated toxicity. Clin. Pharmacol. Ther. 104, 799-802 (2018).
Ciarimboli, G. Membrane transporters as mediators of cisplatin effects and side effects. Scientifica (Cairo) 2012, 473829 (2012).
Filipski, K.K., Mathijssen, R.H., Mikkelsen, T.S., Schinkel, A.H. & Sparreboom, A. Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity. Clin. Pharmacol. Ther. 86, 396-402 (2009).
Sprowl, J.A. et al. Conjunctive therapy of cisplatin with the OCT2 inhibitor cimetidine: influence on antitumor efficacy and systemic clearance. Clin. Pharmacol. Ther. 94, 585-592 (2013).
Nakamura, T., Yonezawa, A., Hashimoto, S., Katsura, T. & Inui, K. Disruption of multidrug and toxin extrusion MATE1 potentiates cisplatin-induced nephrotoxicity. Biochem. Pharmacol. 80, 1762-1767 (2010).
Sprowl, J.A. et al. Cisplatin-induced renal injury is independently mediated by OCT2 and p53. Clin. Cancer Res. 20, 4026-4035 (2014).
Hu, S. et al. Identification of OAT1/OAT3 as contributors to cisplatin toxicity. Clin. Transl. Sci. 10, 412-420 (2017).
More, S.S., Akil, O., Ianculescu, A.G., Geier, E.G., Lustig, L.R. & Giacomini, K.M. Role of the copper transporter, CTR1, in platinum-induced ototoxicity. J. Neurosci. 30, 9500-9509 (2010).
Xu, X., Duan, L., Zhou, B., Ma, R., Zhou, H. & Liu, Z. Genetic polymorphism of copper transporter protein 1 is related to platinum resistance in Chinese non-small cell lung carcinoma patients. Clin. Exp. Pharmacol. Physiol. 39, 786-792 (2012).
Drogemoller, B.I. et al. Association between SLC16A5 genetic variation and cisplatin-induced ototoxic effects in adult patients with testicular cancer. JAMA Oncol. 3, 1558-1562 (2017).
Ciarimboli, G. et al. Organic cation transporter 2 mediates cisplatin-induced oto- and nephrotoxicity and is a target for protective interventions. Am. J. Pathol. 176, 1169-1180 (2010).
Langer, T. et al. Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: results of the European PanCareLIFE cohort study. Eur. J. Cancer 138, 212-224 (2020).
Fox, E. et al. Pantoprazole, an inhibitor of the organic cation transporter 2, does not ameliorate cisplatin-related ototoxicity or nephrotoxicity in children and adolescents with newly diagnosed osteosarcoma treated with methotrexate, doxorubicin, and cisplatin. Oncologist 23, 762-e79 (2018).
Pasquariello, K.Z., Dey, J.M. & Sprowl, J.A. Current understanding of membrane transporters as regulators or targets for cisplatin-induced hearing loss. Mol. Pharmacol. 100, 348-355 (2021).
Sprowl, J.A. et al. Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2. Proc. Natl. Acad. Sci. USA 110, 11199-11204 (2013).
Huang, K.M. et al. Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice. J. Clin. Invest. 130, 4601-4606 (2020).
Sprowl, J.A. et al. A phosphotyrosine switch regulates organic cation transporters. Nat. Commun. 7, 10880 (2016).
Hu, S., Huang, K.M., Adams, E.J., Loprinzi, C.L. & Lustberg, M.B. Recent developments of novel pharmacologic therapeutics for prevention of chemotherapy-induced peripheral neuropathy. Clin. Cancer Res. 25, 6295-6301 (2019).
Feurstein, D., Kleinteich, J., Heussner, A.H., Stemmer, K. & Dietrich, D.R. Investigation of microcystin congener-dependent uptake into primary murine neurons. Environ. Health Perspect. 118, 1370-1375 (2010).
Leblanc, A.F. et al. OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity. J. Clin. Invest. 128, 816-825 (2018).
Sapp, V. et al. Genome-wide CRISPR/Cas9 screening in human iPS derived cardiomyocytes uncovers novel mediators of doxorubicin cardiotoxicity. Sci. Rep. 11, 13866 (2021).
Lee, H.H., Leake, B.F., Kim, R.B. & Ho, R.H. Contribution of organic anion-transporting polypeptides 1A/1B to doxorubicin uptake and clearance. Mol. Pharmacol. 91, 14-24 (2017).
Durmus, S., Naik, J., Buil, L., Wagenaar, E., van Tellingen, O. & Schinkel, A.H. In vivo disposition of doxorubicin is affected by mouse Oatp1a/1b and human OATP1A/1B transporters. Int. J. Cancer. 135, 1700-1710 (2014).
Huang, K.M. et al. Targeting OCT3 attenuates doxorubicin-induced cardiac injury. Proc. Natl. Acad. Sci. USA 118, e2020168118 (2021).
Uddin, M.E., Moseley, A., Hu, S. & Sparreboom, A. Contribution of membrane transporters to chemotherapy-induced cardiotoxicity. Basic Clin. Pharmacol. Toxicol. 130(Suppl. 1), 36-47 (2022).
Saliba, F. et al. Pathophysiology and therapy of irinotecan-induced delayed-onset diarrhea in patients with advanced colorectal cancer: a prospective assessment. J. Clin. Oncol. 16, 2745-2751 (1998).
Conti, J.A. et al. Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J. Clin. Oncol. 14, 709-715 (1996).
Fujita, D., Saito, Y., Nakanishi, T. & Tamai, I. Organic anion transporting polypeptide (OATP)2B1 contributes to gastrointestinal toxicity of anticancer drug SN-38, active metabolite of irinotecan hydrochloride. Drug Metab. Dispos. 44, 1-7 (2016).
Agostino, N.M. et al. Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice. J. Oncol. Pharm. Pract. 17, 197-202 (2011).
Damaraju, V.L. et al. Tyrosine kinase inhibitors reduce glucose uptake by binding to an exofacial site on hGLUT-1: influence on (18) F-FDG PET uptake. Clin. Transl. Sci. 14, 847-858 (2021).
Hadova, K., Mesarosova, L., Kralova, E., Doka, G., Krenek, P. & Klimas, J. The tyrosine kinase inhibitor crizotinib influences blood glucose and mRNA expression of GLUT4 and PPARs in the heart of rats with experimental diabetes. Can. J. Physiol. Pharmacol. 99, 635-643 (2021).
Chu, X., Bleasby, K., Chan, G.H., Nunes, I. & Evers, R. Transporters affecting biochemical test results: creatinine-drug interactions. Clin. Pharmacol. Ther. 100, 437-440 (2016).
Huang, K.M., Uddin, M.E., DiGiacomo, D., Lustberg, M.B., Hu, S. & Sparreboom, A. Role of SLC transporters in toxicity induced by anticancer drugs. Expert. Opin. Drug Metab. Toxicol. 16, 493-506 (2020).
Yamazaki, Y. & Kanekiyo, T. Blood-brain barrier dysfunction and the pathogenesis of Alzheimer's disease. Int. J. Mol. Sci. 18, 1965 (2017).
McCormick, J.W., Ammerman, L., Chen, G., Vogel, P.D. & Wise, J.G. Transport of Alzheimer's associated amyloid-beta catalyzed by P-glycoprotein. PLoS One 16, e0250371 (2021).
Chai, A.B., Hartz, A.M.S., Gao, X., Yang, A., Callaghan, R. & Gelissen, I.C. New evidence for P-gp-mediated export of amyloid-beta PEPTIDES in molecular, blood-brain barrier and neuronal models. Int. J. Mol. Sci. 22, 246 (2020).
Chai, A.B., Leung, G.K.F., Callaghan, R. & Gelissen, I.C. P-glycoprotein: a role in the export of amyloid-beta in Alzheimer's disease? FEBS J. 287, 612-625 (2020).
Brenn, A. et al. Beta-amyloid downregulates MDR1-P-glycoprotein (Abcb1) expression at the blood-brain barrier in mice. Int. J. Alzheimers Dis. 2011, 690121 (2011).
Deo, A.K. et al. Activity of P-glycoprotein, a beta-amyloid transporter at the blood-brain barrier, is compromised in patients with mild Alzheimer disease. J. Nucl. Med. 55, 1106-1111 (2014).
van Assema, D.M. et al. Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients: effect of polymorphisms in the ABCB1 gene. EJNMMI Res. 2, 57 (2012).
Bruckmann, S. et al. Lack of P-glycoprotein results in impairment of removal of beta-amyloid and increased intraparenchymal cerebral amyloid angiopathy after active immunization in a transgenic mouse model of Alzheimer's disease. Curr. Alzheimer Res. 14, 656-667 (2017).
Iwersen-Bergmann, S. et al. Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths. Int. J. Legal Med. 135, 473-482 (2021).
Silva, B., Palmeira, A., Silva, R., Fernandes, C., Guedes de Pinho, P. & Remiao, F. S-(+)-Pentedrone and R-(+)-methylone as the most oxidative and cytotoxic enantiomers to dopaminergic SH-SY5Y cells: role of MRP1 and P-gp in cathinones enantioselectivity. Toxicol. Appl. Pharmacol. 416, 115442 (2021).
Cannon, R.E. et al. Effect of GenX on P-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated protein 2 at the blood-brain barrier. Environ. Health Perspect. 128, 37002 (2020).
Cannon, R.E., Trexler, A.W., Knudsen, G.A., Evans, R.A. & Birnbaum, L.S. Tetrabromobisphenol A (TBBPA) alters ABC transport at the blood-brain barrier. Toxicol. Sci. 169, 475-484 (2019).
Trexler, A.W., Knudsen, G.A., Nicklisch, S.C.T., Birnbaum, L.S. & Cannon, R.E. 2,4,6-Tribromophenol exposure decreases P-glycoprotein transport at the blood-brain barrier. Toxicol. Sci. 171, 463-472 (2019).
Engdahl, E. et al. Bisphenol A inhibits the transporter function of the blood-brain barrier by directly interacting with the ABC transporter breast cancer resistance protein (BCRP). Int. J. Mol. Sci. 22, 5534 (2021).
Walters, D.C. et al. Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use-limiting visual field defects. Pharmacol. Res. Perspect. 7, e00456 (2019).
Police, A., Shankar, V.K. & Murthy, S.N. Role of taurine transporter in the retinal uptake of vigabatrin. AAPS PharmSciTech 21, 196 (2020).
Beltramo, E., Mazzeo, A., Lopatina, T., Trento, M. & Porta, M. Thiamine transporter 2 is involved in high glucose-induced damage and altered thiamine availability in cell models of diabetic retinopathy. Diab. Vasc. Dis. Res. 17, 1479164119878427 (2020).
Porta, M. et al. Variation in SLC19A3 and protection from microvascular damage in type 1 diabetes. Diabetes 65, 1022-1030 (2016).
Feng, Q., Yang, W., Gao, Z., Ruan, X. & Zhang, Y. Up-regulation of P-gp via NF-kappaB activation confers protection against oxidative damage in the retinal pigment epithelium cells. Exp. Eye Res. 181, 367-373 (2019).
Wang, Y. et al. Multidrug resistance protein 1 deficiency promotes doxorubicin-induced ovarian toxicity in female mice. Toxicol. Sci. 163, 279-292 (2018).
Clark, H., Pereira Vera, B., Zhang, Z. & Brayboy, L.M. MDR-1 function protects oocyte mitochondria against the transgenerational effects of nitrogen mustard exposure. Reprod. Toxicol. 98, 252-259 (2020).
Brayboy, L.M., Oulhen, N., Long, S., Voigt, N., Raker, C. & Wessel, G.M. Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology. Reprod. Toxicol. 69, 121-131 (2017).
Brayboy, L.M., Oulhen, N., Witmyer, J., Robins, J., Carson, S. & Wessel, G.M. Multidrug-resistant transport activity protects oocytes from chemotherapeutic agents and changes during oocyte maturation. Fertil. Steril. 100, 1428-1435 (2013).
Clark, H. et al. Dysfunctional MDR-1 disrupts mitochondrial homeostasis in the oocyte and ovary. Sci. Rep. 9, 9616 (2019).
Malone, E.R. et al. Semen and serum platinum levels in cisplatin-treated survivors of germ cell cancer. Cancer Med. 11, 728-734 (2022).
Stephenson, W.T., Poirier, S.M., Rubin, L. & Einhorn, L.H. Evaluation of reproductive capacity in germ cell tumor patients following treatment with cisplatin, etoposide, and bleomycin. J. Clin. Oncol. 13, 2278-2280 (1995).
Klein, D.M., Evans, K.K., Hardwick, R.N., Dantzler, W.H., Wright, S.H. & Cherrington, N.J. Basolateral uptake of nucleosides by Sertoli cells is mediated primarily by equilibrative nucleoside transporter 1. J. Pharmacol. Exp. Ther. 346, 121-129 (2013).
Miller, S.R., McGrath, M.E., Zorn, K.M., Ekins, S., Wright, S.H. & Cherrington, N.J. Remdesivir and EIDD-1931 interact with human equilibrative nucleoside transporters 1 and 2: implications for reaching SARS-CoV-2 viral sanctuary sites. Mol. Pharmacol. 100, 548-557 (2021).
Wijnholds, J. et al. Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J. Exp. Med. 188, 797-808 (1998).
Iwata, K. et al. Effects of genetic variants in SLC22A2 organic cation transporter 2 and SLC47A1 multidrug and toxin extrusion 1 transporter on cisplatin-induced adverse events. Clin. Exp. Nephrol. 16, 843-851 (2012).
Dankers, A.C. et al. Endocrine disruptors differentially target ATP-binding cassette transporters in the blood-testis barrier and affect Leydig cell testosterone secretion in vitro. Toxicol. Sci. 136, 382-391 (2013).
Wang, C. et al. Increased risk for congenital heart defects in children carrying the ABCB1 Gene C3435T polymorphism and maternal periconceptional toxicants exposure. PLoS One 8, e68807 (2013).
Wang, C. et al. Associations between ABCG2 gene polymorphisms and isolated septal defects in a Han Chinese population. DNA Cell Biol. 33, 689-698 (2014).
Cao, Y. et al. Maternal exposure to bisphenol A induces fetal growth restriction via upregulating the expression of estrogen receptors. Chemosphere 287, 132244 (2022).
Endres, C.J., Moss, A.M., Ishida, K., Govindarajan, R. & Unadkat, J.D. The role of the equilibrative nucleoside transporter 1 on tissue and fetal distribution of ribavirin in the mouse. Biopharm. Drug Dispos. 37, 336-344 (2016).
Karbanova, S. et al. Transport of ribavirin across the rat and human placental barrier: roles of nucleoside and ATP-binding cassette drug efflux transporters. Biochem. Pharmacol. 163, 60-70 (2019).
Filia, M.F. et al. Induction of ABCG2/BCRP restricts the distribution of zidovudine to the fetal brain in rats. Toxicol. Appl. Pharmacol. 330, 74-83 (2017).
Szilagyi, J.T., Gorczyca, L., Brinker, A., Buckley, B., Laskin, J.D. & Aleksunes, L.M. Placental BCRP/ABCG2 transporter prevents fetal exposure to the estrogenic mycotoxin zearalenone. Toxicol. Sci. 168, 394-404 (2019).
Sieppi, E., Vahakangas, K., Rautio, A., Ietta, F., Paulesu, L. & Myllynen, P. The xenoestrogens, bisphenol A and para-nonylphenol, decrease the expression of the ABCG2 transporter protein in human term placental explant cultures. Mol. Cell Endocrinol. 429, 41-49 (2016).
Agency for Toxic Substances and Disease Registry (ATSDR) <https://wwwatsdrcdcgov/spl/>.
World Health Organization (WHO) <https://wwwwhoint/news-room/photo-story/photo-story-detail/10-chemicals-of-public-health-concern>.
Podgorski, J. & Berg, M. Global threat of arsenic in groundwater. Science 368, 845-850 (2020).
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Arsenic, metals, fibres, and dusts. IARC Monogr. Eval. Carcinog. Risks Hum. 100, 11-465 (2012).
Naujokas, M.F. et al. The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environ. Health Perspect. 121, 295-302 (2013).
Martinez, V.D. & Lam, W.L. Health effects associated with pre- and perinatal exposure to arsenic. Front. Genet. 12, 664717 (2021).
Roggenbeck, B.A., Banerjee, M. & Leslie, E.M. Cellular arsenic transport pathways in mammals. J. Environ. Sci. (China) 49, 38-58 (2016).
Garbinski, L.D., Rosen, B.P. & Chen, J. Pathways of arsenic uptake and efflux. Environ. Int. 126, 585-597 (2019).
Leslie, E.M. Arsenic-glutathione conjugate transport by the human multidrug resistance proteins (MRPs/ABCCs). J. Inorg. Biochem. 108, 141-149 (2012).
Villa-Bellosta, R. & Sorribas, V. Arsenate transport by sodium/phosphate cotransporter type IIb. Toxicol. Appl. Pharmacol. 247, 36-40 (2010).
Thomas, D.J. et al. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals. Exp. Biol. Med. (Maywood) 232, 3-13 (2007).
Shen, S., Li, X.F., Cullen, W.R., Weinfeld, M. & Le, X.C. Arsenic binding to proteins. Chem. Rev. 113, 7769-7792 (2013).
Banerjee, M., Kaur, G., Whitlock, B.D., Carew, M.W., Le, X.C. & Leslie, E.M. Multidrug resistance protein 1 (MRP1/ABCC1)-mediated cellular protection and transport of methylated arsenic metabolites differs between human cell lines. Drug Metab. Dispos. 46, 1096-1105 (2018).
George, G.N. et al. Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile. J. Inorg. Biochem. 158, 24-29 (2016).
Gailer, J., George, G.N., Pickering, I.J., Prince, R.C., Younis, H.S. & Winzerling, J.J. Biliary excretion of [(GS)(2)AsSe](-) after intravenous injection of rabbits with arsenite and selenate. Chem. Res. Toxicol. 15, 1466-1471 (2002).
Zhou, J.R. et al. Biliary excretion of arsenic by human HepaRG cells is stimulated by selenide and mediated by the multidrug resistance protein 2 (MRP2/ABCC2). Biochem. Pharmacol. 193, 114799 (2021).
Kaur, G. et al. Human red blood cell uptake and sequestration of arsenite and selenite: evidence of seleno-bis(S-glutathionyl) arsinium ion formation in human cells. Biochem. Pharmacol. 180, 114141 (2020).
Manley, S.A. et al. The seleno bis(S-glutathionyl) arsinium ion is assembled in erythrocyte lysate. Chem. Res. Toxicol. 19, 601-617 (2006).
Csanaky, I. & Gregus, Z. Effect of selenite on the disposition of arsenate and arsenite in rats. Toxicology 186, 33-50 (2003).
Abuawad, A., Bozack, A.K., Saxena, R. & Gamble, M.V. Nutrition, one-carbon metabolism and arsenic methylation. Toxicology 457, 152803 (2021).
Kim, J.J., Kim, Y.S. & Kumar, V. Heavy metal toxicity: an update of chelating therapeutic strategies. J. Trace Elem. Med. Biol. 54, 226-231 (2019).
Kosnett, M.J. The role of chelation in the treatment of arsenic and mercury poisoning. J. Med. Toxicol. 9, 347-354 (2013).
Streets, D.G., Horowitz, H.M., Lu, Z., Levin, L., Thackray, C.P. & Sunderland, E.M. Global and regional trends in mercury emissions and concentrations, 2010-2015. Atmos. Environ. 201, 417-427 (2019).
UN Environment Programme. UNEP Global Mercury Partnership, Geneva <https://www.unep.org/resources/publication/global-mercury-assessment-2018?_ga=22426819949682715681646078157-6234203581646078157> (2018). Accessed February 28 2022.
Hsu, W.H. et al. Biomonitoring of exposure to Great Lakes contaminants among licensed anglers and Burmese refugees in Western New York: toxic metals and persistent organic pollutants, 2010-2015. Int. J. Hyg. Environ. Health 240, 113918 (2022).
Chang, C.H. et al. Dietary exposure assessment of methylmercury and polyunsaturated fatty acids in saltwater fish and processed foods among Taiwanese women of child-bearing age and children: a novel core food-matching approach. Chemosphere 262, 128249 (2021).
Li, A. et al. Persistent and toxic chemical pollutants in fish consumed by Asians in Chicago, United States. Sci. Total Environ. 811, 152214 (2022).
Environmental Protection Agency (EPA) <https://www.EPA.gov/international-cooperation/reducing-mercury-pollution-artisanal-and-small-scale-gold-mining>.
Wanyana, M.W. et al. Mercury exposure among Artisanal and small-scale gold miners in four regions in Uganda. J. Health Pollut. 10, 200613 (2020).
Galeano-Paez, C. et al. Dietary exposure to mercury and its relation to cytogenetic instability in populations from "La Mojana" region, northern Colombia. Chemosphere 265, 129066 (2021).
Fuhr, B.J. & Rabenstein, D.L. Nuclear magnetic resonance studies of the solution chemistry of metal complexes. IX. The binding of cadmium, zinc, lead, and mercury by glutathione. J. Am. Chem. Soc. 95, 6944-6950 (1973).
Hughes, W.L. A physicochemical rationale for the biological activity of mercury and its compounds. Ann. NY Acad. Sci. 65, 454-460 (1957).
Simmons-Willis, T.A., Koh, A.S., Clarkson, T.W. & Ballatori, N. Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. Biochem J. 367, 239-246 (2002).
Duelli, R., Enerson, B.E., Gerhart, D.Z. & Drewes, L.R. Expression of large amino acid transporter LAT1 in rat brain endothelium. J. Cereb. Blood Flow Metab. 20, 1557-1562 (2000).
Zimmermann, L.T. et al. Comparative study on methyl- and ethylmercury-induced toxicity in C6 glioma cells and the potential role of LAT-1 in mediating mercurial-thiol complexes uptake. Neurotoxicology 38, 1-8 (2013).
Norseth, T. & Clarkson, T.W. Biotransformation of methylmercury salts in the rat studied by specific determination of inorganic mercury. Biochem. Pharmacol. 19, 2775-2783 (1970).
Zalups, R.K. Molecular interactions with mercury in the kidney. Pharmacol. Rev. 52, 113-143 (2000).
Bridges, C.C., Bauch, C., Verrey, F. & Zalups, R.K. Mercuric conjugates of cysteine are transported by the amino acid transporter system b(0,+): implications of molecular mimicry. J. Am. Soc. Nephrol. 15, 663-673 (2004).
Zalups, R.K., Aslamkhan, A.G. & Ahmad, S. Human organic anion transporter 1 mediates cellular uptake of cysteine-S conjugates of inorganic mercury. Kidney Int. 66, 251-261 (2004).
Zalups, R.K. & Ahmad, S. Homocysteine and the renal epithelial transport and toxicity of inorganic mercury: role of basolateral transporter organic anion transporter 1. J. Am. Soc. Nephrol. 15, 2023-2031 (2004).
Bridges, C.C., Joshee, L. & Zalups, R.K. Multidrug resistance proteins and the renal elimination of inorganic mercury mediated by 2,3-dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid. J. Pharmacol. Exp. Ther. 324, 383-390 (2008).
Khan, M.A. & Wang, F. Mercury-selenium compounds and their toxicological significance: toward a molecular understanding of the mercury-selenium antagonism. Environ. Toxicol. Chem. 28, 1567-1577 (2009).
Takahashi, K., Ruiz Encinar, J., Costa-Fernandez, J.M. & Ogra, Y. Distributions of mercury and selenium in rats ingesting mercury selenide nanoparticles. Ecotoxicol. Environ. Saf. 226, 112867 (2021).
Joshee, L., Kiefer, A., Seney, C., Matta, K.E., Orr, S.E. & Bridges, C.C. Prophylactic supplementation with selenium alters disposition of mercury in aged rats. Exp. Gerontol. 149, 111289 (2021).
Pappas, R.S., Fresquez, M.R., Martone, N. & Watson, C.H. Toxic metal concentrations in mainstream smoke from cigarettes available in the USA. J. Anal. Toxicol. 38, 204-211 (2014).
Satarug, S., Garrett, S.H., Sens, M.A. & Sens, D.A. Cadmium, environmental exposure, and health outcomes. Environ. Health Perspect. 118, 182-190 (2010).
Genchi, G., Sinicropi, M.S., Lauria, G., Carocci, A. & Catalano, A. The effects of cadmium toxicity. Int. J. Environ. Res. Public Health 17, 3782 (2020).
Satarug, S., Vesey, D.A. & Gobe, G.C. Kidney cadmium toxicity, diabetes and high blood pressure: the perfect storm. Tohoku J. Exp. Med. 241, 65-87 (2017).
Sabolic, I., Breljak, D., Skarica, M. & Herak-Kramberger, C.M. Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals 23, 897-926 (2010).
Thevenod, F., Fels, J., Lee, W.K. & Zarbock, R. Channels, transporters and receptors for cadmium and cadmium complexes in eukaryotic cells: myths and facts. Biometals 32, 469-489 (2019).
Thevenod, F. Catch me if you can! Novel aspects of cadmium transport in mammalian cells. Biometals 23, 857-875 (2010).
Gunshin, H. et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482-488 (1997).
Nebert, D.W. & Liu, Z. SLC39A8 gene encoding a metal ion transporter: discovery and bench to bedside. Hum. Genomics 13, 51 (2019).
Tommasini, R. et al. The human multidrug resistance-associated protein functionally complements the yeast cadmium resistance factor 1. Proc. Natl. Acad. Sci. USA 93, 6743-6748 (1996).
Thevenod, F. et al. Substrate- and cell contact-dependent inhibitor affinity of human organic cation transporter 2: studies with two classical organic cation substrates and the novel substrate cd2+. Mol. Pharm. 10, 3045-3056 (2013).
Soodvilai, S., Nantavishit, J., Muanprasat, C. & Chatsudthipong, V. Renal organic cation transporters mediated cadmium-induced nephrotoxicity. Toxicol. Lett. 204, 38-42 (2011).
Garza-Lopez, E., Chavez, J.C., Santana-Calvo, C., Lopez-Gonzalez, I. & Nishigaki, T. Cd(2+) sensitivity and permeability of a low voltage-activated Ca(2+) channel with CatSper-like selectivity filter. Cell Calcium 60, 41-50 (2016).
Miura, S. et al. Involvement of TRPA1 activation in acute pain induced by cadmium in mice. Mol. Pain 9, 7 (2013).
Kovacs, G., Montalbetti, N., Franz, M.C., Graeter, S., Simonin, A. & Hediger, M.A. Human TRPV5 and TRPV6: key players in cadmium and zinc toxicity. Cell Calcium 54, 276-286 (2013).
Wen, X. et al. BCRP/ABCG2 transporter regulates accumulation of cadmium in kidney cells: role of the Q141K variant in modulating nephrotoxicity. Drug Metab. Dispos. 49, 629-637 (2021).
Zwolak, I. The role of selenium in arsenic and cadmium toxicity: an updated review of scientific literature. Biol. Trace Elem. Res. 193, 44-63 (2020).
Evers, R. et al. Disease-associated changes in drug transporters may impact the pharmacokinetics and/or toxicity of drugs: a white paper from the international transporter consortium. Clin. Pharmacol. Ther. 104, 900-915 (2018).