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.
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.
authors.affiliation: 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>
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Brown
authors.forename: Martin
authors.initials: M
authors.lastname: Shaw
authors.forename: Vishal S
authors.initials: VS
authors.lastname: Vaidya
authors.forename: Yuzhao
authors.initials: Y
authors.lastname: Zhou
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Espandiari
authors.forename: Nakissa
authors.initials: N
authors.lastname: Sadrieh
authors.forename: Melvin
authors.initials: M
authors.lastname: Stratmeyer
authors.forename: Joe
authors.initials: J
authors.lastname: Keenan
authors.forename: Cormac G
authors.initials: CG
authors.lastname: Kilty
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: Peter L
authors.initials: PL
authors.lastname: Goering
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D005839:Gentamicins / Q000633:toxicity; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism; D011192:Potassium Dichromate / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015854:Up-Regulation; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D000941:Antigens; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D005839:Gentamicins; D008627:Mercuric Chloride; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid; D011192:Potassium Dichromate; D014443:Tyrosine; D015262:Xenobiotics; C110936:Havcr1 protein, rat; C035812:renal tubular antigen; C002744:3-nitrotyrosine; C496318:Nos2 protein, rat