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.

@article{citeulike:2927935, 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.}, address = {Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993, USA. jun.zhang@fda.hhs.gov <jun.zhang@fda.hhs.gov>}, author = {Zhang, J. and Brown, R. P. and Shaw, M. and Vaidya, V. S. and Zhou, Y. and Espandiari, P. and Sadrieh, N. and Stratmeyer, M. and Keenan, J. and Kilty, C. G. and Bonventre, J. V. and Goering, P. L. }, citeulike-article-id = {2927935}, doi = {http://dx.doi.org/10.1177/0192623308315832}, issn = {1533-1601}, journal = {Toxicologic pathology}, keywords = {biomarker, nephrotoxicity, no, urine}, number = {3}, pages = {397--409}, posted-at = {2008-06-26 03:49:00}, priority = {2}, title = {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.}, url = {http://dx.doi.org/10.1177/0192623308315832}, volume = {36}, year = {2008} }

TY - JOUR ID - citeulike:2927935 L3 - citeulike-article-id:2927935 TI - 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. JF - Toxicologic pathology VL - 36 IS - 3 SP - 397 EP - 409 AD - Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993, USA. jun.zhang@fda.hhs.gov <jun.zhang@fda.hhs.gov> SN - 1533-1601 N2 - 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. KW - biomarker KW - nephrotoxicity KW - no KW - urine AU - Zhang, J AU - Brown, RP AU - Shaw, M AU - Vaidya, VS AU - Zhou, Y AU - Espandiari, P AU - Sadrieh, N AU - Stratmeyer, M AU - Keenan, J AU - Kilty, CG AU - Bonventre, JV AU - Goering, PL PY - 2008/// UR - http://dx.doi.org/10.1177/0192623308315832 ER -