Organic anion transporter 5 renal expression and urinary excretion in rats exposed to mercuric chloride: a potential biomarker of mercury-induced nephropathy.
Mercuric chloride (HgCl(2)) induces acute kidney injury (AKI) affecting glomerular hemodynamics and, more specifically, the pars recta (S3 segment) of the proximal tubule. The organic anion transporter 5 (Oat5) is exclusively localized in the apical membranes of S3 segment. Oat5 urinary excretion was recently proposed as potential early biomarker of ischemic AKI. The aim of this study was to evaluate the renal expression and the urinary excretion of the Oat5 in rats exposed to HgCl(2). Male Wistar rats were treated with a single injection of HgCl(2) at different doses of 0, 0.2, 1 and 5 mg/kg body wt (control, Hg0.2, Hg1 and Hg5 groups). The renal expression of Oat5 was evaluated by immunohistochemistry, Western blotting, and real-time PCR. Oat5 and sodium dicarboxylate cotransporter 1 (NaDC1) abundances and alkaline phosphatase activity (AP) were assayed in urine. An HgCl(2) dose-related decrease in Oat5 mRNA levels and in Oat5 protein levels in renal homogenates was observed. Hg5 rats showed an increase in urinary excretion of Oat5 and NaDC1 as well as alterations of other widely used parameters for renal dysfunction and injury (plasma creatinine, plasma urea, urinary AP activity, kidney weight, histological lesions). In Hg0.2 group only an increase of urinary excretion of Oat5 was observed. The increase of Oat5 urinary excretion in Hg1 group was associated to the beginning of tissular injury. These results suggest that urinary excretion of Oat5 might be an early indicator of mercury-induced nephropathy, which predicts the perturbation before the manifestation of histopathological damages.
Di Giusto
Gisela
G
Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, 2000 Rosario, Argentina.
Torres
Adriana Mónica
AM
D000469:Alkaline Phosphatase / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D029382:Dicarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D014508:Urea / Q000097:blood
D015415:Biomarkers; D029382:Dicarboxylic Acid Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; C490478:Slc13a2 protein, rat; C506835:Slc22a24 protein, rat; D027981:Symporters; D008627:Mercuric Chloride; D014508:Urea; D003404:Creatinine; D000469:Alkaline Phosphatase