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.

Applying a multiscale systems biology approach to study the effect of chronic low-dose exposure to uranium in rat kidneys

“…Similarly, none of the clinical markers assessed in plasma and urine samples, including ions and kidney markers (data not shown), revealed any significant differences that might reflect either a significant metabolic disorder or an adverse health effect associated with these NU exposure conditions. A mean NU concentration in kidney tissue less than 500 ng.g À1 (data not shown) confirmed its tubular accumulation in the chronically contaminated rats and, as previously reported, its non-nephrotoxic level, confirmed by histological observations (Leggett 1989;Dublineau et al 2014;Poisson et al 2014). Moreover, for 1.6 g of kidney mass, the absorbed dose rate in the kidneys of the contaminated rats, was estimated at 9 months of age at 5.4 9 10-7 Gy d-1.…”

Biochemical and histopathological responses of the Swiss albino mice treated with uranyl nitrate and its recovery

“…21 Recently, a chronic uranium exposure study reported that no nephrotoxic effect was found at kidney uranium concentration 6 lg/g of kidney. 22 We observed that the concentration of uranium retained in kidney tissue after administration of UN varies depending on the dose of UN administrated. Animals dosed with, 4 mg/kg of UN after 3 and 5 d retained high levels of uranium in kidney compared with 2 mg/kg of UN and no detectable amount of uranium was found after 14 and 28 d in 2 mg/kg of UNtreated animals.…”

Intracellular uranium distribution: Comparison of cryogenic fixation versus chemical fixation methods for SIMS analysis

“…This observation could be documented by a lesser binding to the macromolecules within the cytoplasm (Bresson et al, ; Frelon, Mounicou, Lobinski, Gilbin, & Simon, ; Ortega et al, ; Perrin, Carmona, Roudeau, & Ortega, ). In addition, we have previously shown from in vivo experiments i using SIMS microscopy that uranium is heterogeneously distributed in the nephron and localized mainly in cell nuclei of proximal convoluted tubules (Poisson et al, ; Tessier et al, ). Similar uranium distribution has been observed using different imaging technic in case of acute renal contamination in rats (Homma‐Takeda et al, ).…”