Differences in Immunolocalization of Kim-1, RPA-1, and RPA-2 in Kidneys of Gentamicin-, Cisplatin-, and Valproic Acid-Treated Rats: Potential Role of iNOS and Nitrotyrosine

The present study compared the immunolocalization of Kim-1, renal papillary antigen (RPA)-1, and RPA-2 with that of inducible nitric oxide synthase (iNOS) and nitrotyrosinein kidneys of gentamicin sulfate ( Gen)- and cisplatin (Cis)-treated rats. The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosinewas evaluated by dosing rats with valproic acid(VPA). Sprague-Dawley (SD) rats were injected subcutaneously (sc) with 100 mg/kg/day of Genfor six or fourteen days; a single intraperitoneal (ip) dose of 1, 3, or 6 mg/kg of Cis; or 650 mg/kg/day of VPA (ip) for four days. In Gen-treated rats, Kim-1 was expressed in the epithelial cells, mainly in the S1/S2 segments but less so in the S3 segment, and RPA-1 was increased in the epithelial cells of collecting ducts (CD) in the cortex. Spatial expression of iNOS or nitrotyrosinewith Kim-1 or RPA-1 was detected. In Cis-treated rats, Kim-1 was expressed only in the S3 segment cells, and RPA-1 and RPA-2 were increased in the epithelial cells of medullary CD or medullary loopof Henle(LH), respectively. Spatial expression of iNOS or nitrotyrosinewith RPA-1 or RPA-2 was also identified. These findings suggest that peroxynitriteformation may be involved in the pathogenesis of Genand Cis nephrotoxicity and that Kim-1, RPA-1, and RPA-2 have the potential to serve as site-specific biomarkers for Genor Cis AKI.