No 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.

With the future aim of elucidating the unknown structures of estrogen degradation products, we characterized the dissociation pathways of protonated estrone (E1) under collisional activation in liquid chromatography/tandem mass spectrometry (LC/MS/MS) experiments employing a quadrupole time-of-flight mass spectrometer. Positive ion and negative ion modes give information on the protonated and deprotonated molecules and their product ions. The mass spectra of estrone methyl ether (CH(3)-E1) and estrone-d(4) (E1-d(4)) were compared with that of E1 in order (i) to elucidate the dissociation mechanisms of protonated and deprotonated molecules and (ii) to propose likely structures for each product ions. The positive ion acquisition mode yielded more fragmentation. The mass spectra of E1 were compared with those of estradiol (E2), estriol (E3) and 17-ethynylestradiol (EE2). This comparison allowed the identification of marker ions for each ring of the estrogenic structure. Accurate mass measurements have been carried out for all the identified ions. The resulting ions revealed to be useful for the characterization of structural modifications induced by photolysis on each ring of the estrone molecule. These results are very promising for the determination of new metabolites in the environment.