title: Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium.
abstract: Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant.
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire, Direction de la Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, F-92262 Fontenay-aux-Roses, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rouas
authors.forename: Johanna
authors.initials: J
authors.lastname: Stefani
authors.forename: Stéphane
authors.initials: S
authors.lastname: Grison
authors.forename: Line
authors.initials: L
authors.lastname: Grandcolas
authors.forename: Cédric
authors.initials: C
authors.lastname: Baudelin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dublineau
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.forename: Yann
authors.initials: Y
authors.lastname: Gueguen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004347:Drug Interactions; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D007610:Kallikreins / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D053495:Osteopontin / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014501:Uranium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D014508:Urea / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D003404:Creatinine; D005839:Gentamicins; D007610:Kallikreins; D053495:Osteopontin; D011506:Proteins; D014501:Uranium; D014508:Urea; C110936:Havcr1 protein, rat