title: Chronic uranium exposure dose-dependently induces glutathione in rats without any nephrotoxicity.
abstract: Uranium is a heavy metal naturally found in the earth's crust that can contaminate the general public population when ingested. The acute effect and notably the uranium nephrotoxicity are well known but knowledge about the effect of chronic uranium exposure is less clear. In a dose-response study we sought to determine if a chronic exposure to uranium is toxic to the kidneys and the liver, and what the anti-oxidative system plays in these effects. Rats were contaminated for 3 or 9 months by uranium in drinking water at different concentrations (0, 1, 40, 120, 400, or 600 mg/L). Uranium tissue content in the liver, kidneys, and bones was linear and proportional to uranium intake after 3 and 9 months of contamination; it reached 6 μg per gram of kidney tissues for the highest uranium level in drinking water. Nevertheless, no histological lesions of the kidney were observed, nor any modification of kidney biomarkers such as creatinine or KIM-1. After 9 months of contamination at and above the 120-mg/L concentration of uranium, lipid peroxidation levels decreased in plasma, liver, and kidneys. Glutathione concentration increased in the liver for the 600-mg/L group, in the kidney it increased dose dependently, up to 10-fold, after 9 months of contamination. Conversely, chronic uranium exposure irregularly modified gene expression of antioxidant enzymes and activities in the liver and kidneys. In conclusion, chronic uranium exposure did not induce nephrotoxic effects under our experimental conditions, but instead reinforced the antioxidant system, especially by increasing glutathione levels in the kidneys.
authors: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX , Fontenay-aux-Roses , France.
authors: C
authors: C
authors: Poisson
authors: J
authors: J
authors: Stefani
authors: L
authors: L
authors: Manens
authors: O
authors: O
authors: Delissen
authors: D
authors: D
authors: Suhard
authors: C
authors: C
authors: Tessier
authors: I
authors: I
authors: Dublineau
authors: Y
authors: Y
authors: Guéguen
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000096:biosynthesis*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014501:Uranium / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014501:Uranium; D005978:Glutathione
keywords: antioxidant system; internal contamination; kidney; liver; radionuclide; rat