{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC22A8, also known as OAT3, is a renal basolateral organic anion transporter that plays a central role in the disposition of a vast array of endogenous and exogenous organic anions. Expressed predominantly in the proximal tubule cells of the kidney, SLC22A8 facilitates the uptake of numerous clinically important drugs—including statins, antiviral agents, antibiotics, and anticancer compounds—as well as endogenous metabolites such as tryptophan catabolites. This transporter is critical for the renal elimination of compounds such as pravastatin and rosuvastatin and is implicated in the clearance of uremic toxins, with genetic variability influencing substrate specificity and transport efficiency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe expression and function of SLC22A8 are tightly regulated by both genetic and post‐translational mechanisms. Its promoter region contains critical binding sites for transcription factors (for example, HNF1α), which ensure its proximal tubule–specific expression. Furthermore, several intracellular signaling pathways—including those activated by angiotensin II and protein kinase cascades—modulate SLC22A8 function by influencing transporter trafficking, endocytosis, SUMOylation, and ubiquitination. Agents such as dexamethasone can exert dual effects by competitively inhibiting substrate binding while, upon cellular entry, enhancing transporter expression via pathways involving serum- and glucocorticoid-inducible kinases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic polymorphisms in SLC22A8 contribute substantially to interindividual differences in drug handling. Functional variants have been linked to altered transport kinetics for several therapeutic agents, including edaravone sulfate, topotecan, and cefotaxime, as well as for anticancer drugs like bendamustine. In addition, the inhibitory effects of commonly coadministered compounds—such as nonsteroidal anti‐inflammatory drugs and proton pump inhibitors—on SLC22A8 can lead to significant drug–drug interactions and modifications of urate handling in hyperuricemia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_fs", "start_ref": "16", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond drug excretion, SLC22A8 is pivotal in the renal handling of endogenous compounds that modulate systemic metabolic homeostasis. It serves as a key mediator for the uptake and clearance of dicarboxylates and tryptophan metabolites—such as xanthurenic and kynurenic acids—which are implicated in the regulation of energy metabolism and may signal changes in the tricarboxylic acid cycle flux. Alterations in SLC22A8 activity can thereby influence remote sensing and signaling processes that coordinate inter-organ communication, with potential implications for endothelial function and the body’s response to uremic toxins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe multifaceted roles of SLC22A8 have clear clinical implications. Altered transporter function or expression is associated with conditions such as acute kidney injury, hypertension, and impaired drug excretion—all of which can increase the risk of adverse drug reactions. In addition, drug–drug interactions can arise when compounds like vindesine and benzofuran-based antiarrhythmics inhibit SLC22A8, further compromising renal clearance. 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"}, {"type": "b", "children": [{"type": "t", "text": "Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharm Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/b:pham.0000012153.71993.cb"}], "href": "https://doi.org/10.1023/b:pham.0000012153.71993.cb"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14984259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14984259"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Andrew R Erdman, Lara M Mangravite, Thomas J Urban, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human organic anion transporter 3 (OAT3; SLC22A8): genetic variation and functional genomics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00272.2005"}], "href": "https://doi.org/10.1152/ajprenal.00272.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16291576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16291576"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ryota Kikuchi, Hiroyuki Kusuhara, Naka Hattori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the expression of human organic anion transporter 3 by hepatocyte nuclear factor 1alpha/beta and DNA methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.106.025494"}], "href": "https://doi.org/10.1124/mol.106.025494"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16793932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16793932"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "A S Windass, S Lowes, Y Wang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Reduced renal clearance of cefotaxime in asians with a low-frequency polymorphism of OAT3 (SLC22A8)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharm Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jps.23581"}], "href": "https://doi.org/10.1002/jps.23581"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23649425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23649425"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Rym Chioukh, Marie-Sophie Noel-Hudson, Sandy Ribes, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Renal human organic anion transporter 3 increases the susceptibility of lymphoma cells to bendamustine uptake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00467.2014"}], "href": "https://doi.org/10.1152/ajprenal.00467.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25477469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25477469"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jiří Vávra, Andrea Mančíková, Kateřina Pavelcová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional Characterization of Rare Variants in OAT1/"}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SLC22A6"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and OAT3/"}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SLC22A8"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Urate Transporters Identified in a Gout and Hyperuricemia Cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells11071063"}], "href": "https://doi.org/10.3390/cells11071063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35406626"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35406626"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Marcel Kaufhold, Katharina Schulz, Davorka Breljak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential interaction of dicarboxylates with human sodium-dicarboxylate cotransporter 3 and organic anion transporters 1 and 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00169.2011"}], "href": "https://doi.org/10.1152/ajprenal.00169.2011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21865262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21865262"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Yuichi Uwai, Emi Honjo "}, {"type": "b", "children": [{"type": "t", "text": "Transport of xanthurenic acid by rat/human organic anion transporters OAT1 and OAT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Biotechnol Biochem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1271/bbb.130178"}], "href": "https://doi.org/10.1271/bbb.130178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23832370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23832370"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Hiroshi Watanabe, Yoshiaki Sakaguchi, Ryusei Sugimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human organic anion transporters function as a high-capacity transporter for p-cresyl sulfate, a uremic toxin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Nephrol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10157-013-0902-9"}], "href": "https://doi.org/10.1007/s10157-013-0902-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24185403"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24185403"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Giane Favretto, Lauro M Souza, Paulo C Gregório, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Organic Anion Transporters in the Uptake of Protein-Bound Uremic Toxins by Human Endothelial Cells and Monocyte Chemoattractant Protein-1 Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Vasc Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000468542"}], "href": "https://doi.org/10.1159/000468542"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28472795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28472795"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Jelle Vriend, Charlotte A Hoogstraten, Kevin R Venrooij, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Organic anion transporters 1 and 3 influence cellular energy metabolism in renal proximal tubule cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/hsz-2018-0446"}], "href": "https://doi.org/10.1515/hsz-2018-0446"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30653465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30653465"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Neema Jamshidi, Sanjay K Nigam "}, {"type": "b", "children": [{"type": "t", "text": "Drug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-022-21091-w"}], "href": "https://doi.org/10.1038/s41598-022-21091-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36316339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36316339"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yun-Feng Han, Xiao-Han Fan, Xiao-Jian Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of intergenic polymorphism of organic anion transporter 1 and 3 genes with hypertension and blood pressure response to hydrochlorothiazide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hypertens (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ajh.2010.191"}], "href": "https://doi.org/10.1038/ajh.2010.191"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21164499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21164499"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Christina Preising, Reinhard Schneider, Michael Bucher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Expression of Renal Organic Anion Transporters OAT1 and OAT3 in a Model of Ischemia/Reperfusion Injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000430328"}], "href": "https://doi.org/10.1159/000430328"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26277839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26277839"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "David Martinez, Kienana Muhrez, Jean-Baptiste Woillard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endogenous Metabolites-Mediated Communication Between OAT1/OAT3 and OATP1B1 May Explain the Association Between SLCO1B1 SNPs and Methotrexate Toxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacol Ther (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cpt.1008"}], "href": "https://doi.org/10.1002/cpt.1008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29285751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29285751"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Chenrong Huang, Fan Xia, Ling Xue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coadministration of vindesine with high-dose methotrexate therapy increases acute kidney injury via BCRP, MRP2, and OAT1/OAT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Chemother Pharmacol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00280-019-03972-6"}], "href": "https://doi.org/10.1007/s00280-019-03972-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31691080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31691080"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Heng Lin Tan, Lloyd Wei Tat Tang, Sheng Yuan Chin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigation of the arcane inhibition of human organic anion transporter 3 by benzofuran antiarrhythmic agents."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Pharmacokinet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dmpk.2021.100390"}], "href": "https://doi.org/10.1016/j.dmpk.2021.100390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33836300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33836300"}]}]}]}