[Show abstract][Hide abstract] ABSTRACT: The present study was conducted to clarify the interference of selenomethionine (SeMet) on methylmercury (MeHg) toxicity through the evaluation of changes in biomarkers of exposure and effect in rats exposed to MeHg and co-exposed to MeHg and SeMet. Male Wistar rats received two intraperitoneally (i.p.) administrations, either MeHg (1.5mg/kg body weight), SeMet alone (1mg/kg body weight) or combined MeHg and SeMet, followed by 3 weeks of rat urine collection and neurobehavioural assays. The effects of different administrations were investigated by the quantification of total mercury in kidney and brain, analysis of urinary porphyrins, determination of hepatic GSH and evaluation of motor activity functions (rearing and ambulation). MeHg exposure resulted in a significant increase of urinary porphyrins during the 3 weeks of rat urine collection, where as it caused a significant decrease in motor activity only at the first day after cessation of rat exposure. Additionally, SeMet co-exposure was able to normalize the porphyrins excretion, and a tendency to restore rat motor activity was observed, on the first day after cessation of exposure. Brain and kidney mercury levels increased significantly in rats exposed to MeHg; however, in co-exposed rats to SeMet no significant changes in Hg levels were found as compared to rats exposed to MeHg alone. Hence, the present study shows that urinary porphyrins are sensitive and persistent indicators of MeHg toxicity and demonstrates for the first time that SeMet reduces its formation. Finally, these results confirm that the mechanism of interaction between SeMet and MeHg cannot be explained by the reduction of Hg levels in target organs and suggestions are made to clarify the interference of SeMet on MeHg toxicity.
[Show abstract][Hide abstract] ABSTRACT: Risk prevention of human exposure against n-hexane neurotoxicity is relevant towards the protective measures to be proposed in occupational toxicology. Metabolic studies have identified 2,5-hexanedione (2,5-HD) as the main neurotoxic metabolite of n-hexane, which reacts with amino groups of lysine in axonal neurofilaments forming 2,5-dimethylpyrrole adducts, which are responsible for n-hexane neurotoxicity. In the present study, we have investigated the interaction of zinc with 2,5-HD, by correlating the decrease of pyrrole derivatives excretion with changes of neurobehavioral effects. Two subchronic experiments (11 and 8 weeks of exposure) were performed in Wistar rats exposed to different doses of 2,5-HD (200, 400 mg/kg per day) and to the mixture of 2,5-HD + zinc acetate (200 + 300 mg/kg per day) and (400 + 500 mg/kg per day). The results obtained show a significant increase in the excretion of pyrroles in the groups exposed to 2,5-HD alone as compared to controls, and a significant decrease in the excretion of pyrrole derivatives in the groups of rats co-exposed to 2,5-HD + zinc acetate when compared to the rats exposed to 2,5-HD alone. These biochemical changes were immediately evident after the first day of exposure. Simultaneously, neurobehavioral testing (rearing and ambulation in open field) was performed weekly in the same groups of rats. The results demonstrated a significant decrease in neurobehavioral dysfunction in rats co-exposed to 2,5-HD and zinc acetate. At the end of the exposure period, pyrroles levels returned to control values progressively, and the recovery of the neurotoxic effects was gradually established depending on the dose of exposure. The results suggest that zinc is a potential chemo-protector against 2,5-HD neurotoxicity which was identified by neurobehavioral testing. Moreover, pyrrole derivatives are good predictive biochemical biomarkers of 2,5-HD exposure and could be used as a complementary tool to characterize its neurotoxic effects.
[Show abstract][Hide abstract] ABSTRACT: The interaction of zinc(II) on the toxicokinetics of 2,5-hexanedione (2,5-HD), the ultimate toxic metabolite of n-hexane, was performed by quantifying the changes of two urinary biomarkers, free 2,5-HD and pyrrole derivatives, in rats exposed to 2,5-HD and to 2,5-HD plus zinc acetate. Eight groups of Wistar rats were exposed for 4 days (dietary and intraperitoneally) to 2,5-HD, zinc acetate and 2,5-HD plus zinc acetate and the 24 h urine was used to determine the excretion of these biomarkers. On comparing the results obtained by the two routes of exposure with different doses of 2,5-HD and zinc acetate, it was observed that there was a significant decrease (P<0.05) in the excretion of free 2,5-HD and pyrroles derivatives in rats exposed to the chemical mixture, when compared with the excretion of these biomarkers in rats exposed to 2,5-HD alone. To evaluate the mechanism of this interaction, further experiments were performed using one group of rat dietary pre-exposed to zinc acetate followed by 2,5-HD exposure. The results of our experiment suggest that zinc protect proteins of pyrrolization by coordination to amino groups, with the subsequent inhibition of protein cross-linking responsible by 2,5-HD neurotoxicity.