title: Stable and episodic/bolus patterns of methylmercury exposure on mercury accumulation and histopathologic alterations in the nervous system.
abstract: The main purpose of the present study was to compare the blood and brain mercury (Hg) accumulation and neurological alterations in adult male and pregnant female/fetal rats following stable and episodic/bolus patterns of methylmercury (MeHg) exposure. In addition, MeHg accumulation in the human body was estimated by a one-compartment model using three different patterns of MeHg exposure. In the adult male rat experiment, doses of 0.3 and 1.5mg MeHg/kg/day were orally administered to the stable groups for 5 weeks, while 7-fold higher doses of 2.1 and 10.5mg MeHg/kg/once a week were administered to the bolus groups. The blood Hg levels increased constantly in the stable groups, but increased with repeated waves in the bolus groups. At completion of the experiment, there were no significant differences in the brain Hg concentrations or neurological alterations between the stable and bolus groups, when the total doses of MeHg were the same. In the pregnant female rat experiment, a dose of 1mg MeHg/kg/day was administered orally to the stable group for 20 days (until 1day before expected parturition), while a 5-fold higher dose of 5mg MeHg/kg/once every 5 days was administered to the bolus group. In the brains of the maternal/fetal rats, there were no significant differences in the Hg concentrations and neurological alterations between the stable and bolus groups. The mean Hg concentrations in the fetal brains were approximately 2-fold higher than those in the maternal brains for both stable and bolus groups. Using the one-compartment model, the Hg accumulation curves in humans at doses of 7µg MeHg/day, 48µg MeHg/once a week, and 96µg MeHg/once every 2 weeks were estimated to be similar, while the bolus groups showed dose-dependent amplitudes of repeated waves. These results suggest that stable and episodic/bolus patterns of MeHg exposure do not cause differences in Hg accumulation in the blood and brain, or in neurological alterations, when the total doses are the same.
authors.affiliation: National Institute for Minamata Disease, Kumamoto, Japan; Universidade Federal do Oeste do Pará, ICED-PPGBIO-PPGRNA-LABBEX, Santarém, Brazil. Electronic address: sakamoto@nimd.go.jp.
authors.forename: Mineshi
authors.initials: M
authors.lastname: Sakamoto
authors.affiliation: Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat "Rovira I Virgili", Reus, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Domingo
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Universidade Federal do Oeste do Pará, ICED-PPGBIO-PPGRNA-LABBEX, Santarém, Brazil.
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: Oliveira
authors.affiliation: Universidade Federal do Oeste do Pará, ICED-PPGBIO-PPGRNA-LABBEX, Santarém, Brazil.
authors.forename: Sandra L F
authors.initials: SL
authors.lastname: Sarrazin
authors.affiliation: National Institute for Minamata Disease, Kumamoto, Japan.
authors.forename: Komyo
authors.initials: K
authors.lastname: Eto
authors.affiliation: Akita University School of Medicine, Akita, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Murata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008628:Mercury / Q000097:blood / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000097:blood / Q000378:metabolism*; D008954:Models, Biological; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008767:Methylmercury Compounds; D008628:Mercury
keywords: Bolus; Exposure pattern; Mercury accumulation; Methylmercury; Neuronal alteration; Stable