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.