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.
Laboratory of Toxicology, Faculty of Pharmacy, Av. das Forças Armadas, 1600, Lisbon, Portugal.
M L
ML
Mateus
A P
AP
dos Santos
M C
MC
Batoréu
D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006588:Hexanones / Q000493:pharmacokinetics* / Q000633:toxicity* / Q000652:urine; D007274:Injections, Intraperitoneal; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D009498:Neurotoxins / Q000493:pharmacokinetics* / Q000633:toxicity* / Q000652:urine; D011758:Pyrroles / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D019345:Zinc Acetate / Q000494:pharmacology*
D015415:Biomarkers; D006588:Hexanones; D009498:Neurotoxins; D011758:Pyrroles; C011269:2,5-hexanedione; D019345:Zinc Acetate