Immunolocalization of Kim-1, RPA-1, and RPA-2 in Kidney of Gentamicin-, Mercury-, or Chromium-Treated Rats: Relationship to Renal Distributions of iNOS and Nitrotyrosine

Abstract

Immunohistochemical studies for kidney injury molecule-1 (Kim-1), renal papillary antigen-1 (RPA-1), and renal papillary antigen-2 (RPA-2) were conducted to explore their relationship to inducible nitric oxide synthase (iNOS) and nitrotyrosine expression. Male Sprague-Dawley rats were exposed to gentamicin (100 mg/kg/day Gen, sc, for 3 days), mercury (0.25 mg Hg/kg, iv, single dose), or chromium (5 mg Cr/kg, sc, single dose) and kidney tissue was examined 24 hours or 72 hours after the last dose of the nephrotoxicant. Another group of kidneys was evaluated 24 hours after rats were administered 3 daily doses (50, 100, 150, 200, or 300 mg/kg/day) of Gen. Gen-and Cr-treated rats exhibited increased immunoreactivity of Kim-1, RPA-1, and RPA-2 largely in the S1/S2 segments and to a lesser extent in the S3 segments of the proximal tubule of the kidney, whereas Hg-treated rats showed increased immunoreactivity of Kim-1, RPA-1, and RPA-2 in the S3 segments. Up-regulation of Kim-1, RPA-1, and RPA-2 expression correlated with injured tubular epithelial cells and also correlated with immunoreactivity of iNOS and nitrotyrosine. It is possible that iNOS activation with nitrotyrosine production in injured nephron segments may be involved in the induction of Kim-1, RPA-1, and RPA-2 following exposure to nephrotoxicants.

Phenothiazine Inhibitors of TLKs Affect Double-Strand Break Repair and DNA Damage Response Recovery and Potentiate Tumor Killing with Radiomimetic Therapy

“…To further establish this, we looked at the presence of RPA foci, which is indicative of stalled forks. 25 As expected from the large number of proliferating cells (PCNA positive) in control tumors, RPA1 staining was very strong and particularly in focal areas. RPA1 staining in tumors from doxo-treated mice was interesting.…”

Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine

“…Negative control slides were prepared by replacing the primary antiserum with PBS. A lung slide was used as the positive control for iNOS [Zhang et al, 2008].…”

Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats

“…Immunostaining for these kidney injury biomarkers and TdT-mediated dUTP nick end labeling staining for apoptosis have been previously described. 15,35 Statistics One-way analysis of variance or t-tests were used to compare treatment groups with time-matched controls. For nonparametric data, the Mann-Whitney rank-sum test was used.…”