title: Biomarkers of exposure and effect as indicators of the interference of selenomethionine on methylmercury toxicity.
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.
authors.affiliation: Centro de Estudos de Ciências Farmacêuticas, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Ana P M
authors.initials: AP
authors.lastname: dos Santos
authors.forename: M Luísa
authors.initials: ML
authors.lastname: Mateus
authors.forename: C M L
authors.initials: CM
authors.lastname: Carvalho
authors.forename: M Camila C
authors.initials: MC
authors.lastname: Batoréu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D020262:Mercury Poisoning, Nervous System / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011166:Porphyrins / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012645:Selenomethionine / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D008767:Methylmercury Compounds; D011166:Porphyrins; D012645:Selenomethionine; C020771:methylmercury hydroxide; D005978:Glutathione