Correlation of Neurobehavioral testing with biomarkers of excretion

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-hexa

Evidence for zinc protection against 2,5-hexanedione toxicity by co-exposure of rats to zinc chloride

The protective role of zinc against the toxic effects of 2,5-hexanedione (2,5-HD), the main neurotoxic metabolite of n-hexane, was investigated by studying the interference of zinc on the toxicokinetics of 2,5-HD, Six groups of Wistar rats were exposed for 3 days to diets containing 2,5-HD, zinc chloride and 2,5-HD+zinc chloride. The amounts of pyrroles and free and total 2,5-HD in urine were determined using Ehrlichs's reagent and gas chromatography/flame ionization detection, respectively. The results show that after the first day of co-exposure (ZnCl2+2,5-HD) there was a significant decrease in the excretion of pyrroles and free 2,5-HD in rats exposed to the chemical mixture when compared to the pyrroles and free 2,5-HD excreted in rats exposed to 2,5-HD alone. However, no significant decrease was observed in the urinary excretion of total 2,5-HD (free 2,5-HD + preformed 2,5-HD). Suggestions are made about the role played by this metal ion in inhibiting pyrrole formation. Copyright (C) 2000 John Wiley & Sons, Ltd

Interaction of zinc on biomarker responses in rats exposed to 2,5-hexanedione by two routes of exposure

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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved