{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T12:43:56Z","timestamp":1792327436787,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Vet Emergen Crit Care"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate and compare the enantiomer\u2010specific nephrotoxicity of tartaric acid (TTA) in Madin\u2013Darby canine kidney (MDCK) cells and human kidney (HK\u20102) cells. Secondary aims were to determine the enantiomeric\u2010specific TTA accumulation to induce these effects through distinct influx and efflux pathways via organic anion transporter (OAT)\u20101 and OAT\u20104. Subsequently, a critical objective was to determine the mitochondrial mechanisms of toxicity via citrate synthase inhibition and assess supplemental substrate mitigation within this reaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>In vitro concentration\u2013response experiments and transporter transfection studies using racemic and enantiomeric forms of TTA in canine and human immortalized renal cell lines over a 48\u2010h exposure period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>School of Pharmacy biomedical research laboratory and tissue culture facility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals\/Samples<\/jats:title>\n                    <jats:p>Immortalized MDCK and HK\u20102 proximal tubule epithelial cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>MDCK and HK\u20102 cells were treated with 5\u201350\u00a0mmol\/L of racemic or enantiomeric TTA for 48\u00a0h. Cotreatment of 0.08\u00a0mmol\/L oxaloacetate (OAA) was used to assess the mitigation of citrate synthase inhibition. Additional transporter transfection experiments were conducted using probenecid (PBD) as a cotreatment to gain a greater understanding of TTA accumulation and toxicity prevention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Cellular ATP levels and citrate synthase activity were measured. L\u2010Tartaric acid (L\u2010TTA) caused significant ATP depletion (8.5%\u201324.8%) and citrate synthase inhibition (36.5%\u201345.0%) in MDCK cells but not in HK\u20102 cells, suggesting species\u2010specific toxicity. OAT\u20104 transfection reduced ATP loss by 8.0%\u201311.2% after L\u2010TTA exposure. Cotreatment with PBD reduced cytotoxic L\u2010TTA effects by 11.7%, suggesting that OAT\u20101 uptake and insufficient OAT\u20104 efflux are central to TTA accumulation. Cotreatment with OAA rescued ATP loss by 15.6%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>L\u2010TTA is a species\u2010 and enantiomer\u2010specific nephrotoxicant in dogs resulting from a lack of transporter\u2010mediated efflux and subsequent citrate synthase inhibition. OAT\u20101 inhibition or OAT\u20104 transfection mitigates toxicity, supporting a transporter\u2010driven mechanism for TTA accumulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/vec.70152","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:24:28Z","timestamp":1786724668000},"page":"603-611","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of Tartaric Acid Enantiomer\u2010Specific Nephrotoxicity and Citrate Synthase Inhibition in Madin\u2013Darby Canine Kidney Cells In Vitro"],"prefix":"10.1111","volume":"36","author":[{"given":"Penelope","family":"Pando","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy Massachusetts College of Pharmacy and Health Sciences  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Q.","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy Massachusetts College of Pharmacy and Health Sciences  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell G.","family":"Neitlich","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy Massachusetts College of Pharmacy and Health Sciences  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg M.","family":"Landry","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy Massachusetts College of Pharmacy and Health Sciences  Boston Massachusetts 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