title: Antioxidant status in rat kidneys after coexposure to uranium and gentamicin.
abstract: Uranium (U) accumulates and produces its toxic effects preferentially in the kidneys, especially in the proximal tubular structure. U disturbs the balance of pro-/antioxidants in the renal cortex after acute exposure. Other nephrotoxic agents, such as medications, also cause oxidative stress, but the effects of coexposure are not known. The aim of this study was to analyze the effect of chronic exposure to U and acute gentamicin treatment on the pro- and antioxidant status of the renal cortex of rats. Animals were chronically exposed (9 months) to a nonnephrotoxic level of U (40 mg/L) and then treated with daily injections of gentamicin at a range of doses (0, 5, 25, 100, and 150 mg/kg) during the last week of contamination. We studied changes in the gene expression, protein expression, and enzyme activity of key factors involved in the pro-/antioxidant balance in the renal cortex. At and above a dose of 100 mg/kg, gentamicin decreased the messenger RNA (mRNA) levels of catalase (CAT), copper/zinc superoxide dismutase (SOD) and increased the mRNA levels of heme oxygenase-1 in contaminated rats. This treatment decreased CAT activity, but did not significantly change the SOD protein level. Chronic exposure to U did not worsen these effects in our experimental conditions. In conclusion, gentamicin treatment disturbed the oxidative balance in our model's renal cortex, but the chronic exposure to U at this nonnephrotoxic level did not appear to reinforce these effects.
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Fontenay-aux-Roses, France.
authors.forename: C
authors.initials: C
authors.lastname: Poisson
authors.forename: C
authors.initials: C
authors.lastname: Rouas
authors.forename: L
authors.initials: L
authors.lastname: Manens
authors.forename: I
authors.initials: I
authors.lastname: Dublineau
authors.forename: Y
authors.initials: Y
authors.lastname: Gueguen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism*; D004359:Drug Therapy, Combination; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D015227:Lipid Peroxidation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014501:Uranium / Q000633:toxicity*
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005839:Gentamicins; D014501:Uranium; D005979:Glutathione Peroxidase
keywords: Depleted uranium; chronic exposure; gentamicin; kidney; oxidative stress