title: Assessment of bioaccumulation and neurotoxicity in rats with portacaval anastomosis and exposed to manganese phosphate: a pilot study.
abstract: The use of the additive methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline has resulted in increased attention to the potential toxic effects of manganese (Mn). Hypothetically, people with chronic liver disease may be more sensitive to the adverse neurotoxic effects of Mn. In this work, bioaccumulation of Mn, as well as histopathology and neurobehavioral damage, in end-to-side portacaval anastomosis (PCA) rats exposed to Mn phosphate via inhalation was investigated. During the week before the PCA operation, 4 wk after the PCA operation, and at the end of exposure, the rats were subjected to a locomotor evaluation (day-night activities) using a computerized autotrack system. Then a group of 6 PCA rats (EXP) was exposed to 3050 microg m(-3) (Mn phosphate) for 8 h/day, 5 days/wk for 4 consecutive weeks and compared to a control group (CON), 7 PCA rats exposed to 0.03 microg m(-3). After exposure, the rats were euthanized and Mn content in tissues and organs was determined by neutron activation analysis. The manganese concentrations in blood (0.05 microg/g vs. 0.02 microg/g), lung (1.32 microg/g vs. 0.24 microg/g), cerebellum (0.85 microg/g vs. 0.64 microg/g), frontal cortex (0.87 microg/g vs. 0.61 microg/g), and globus pallidus (3.56 microg/g vs. 1.33 microg/g) were significantly higher in the exposed group compared to the control group (p <.05). No difference was observed in liver, kidney, testes, and caudate putamen between the two groups. Neuronal cell loss was assessed by neuronal cell counts. The loss of cells in globus pallidus and caudate putamen as well as in frontal cortex was significantly higher (p <.05) for the EXP group. Assessment of the locomotor activities did not reveal any significant difference. This study constitutes a first step toward our understanding of the potential adverse effects of Mn in sensitive populations.
authors.affiliation: Human Toxicology Research Group and Department of Environmental and Occupational Medicine, University of Montreal, Quebec, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Salehi
authors.forename: G
authors.initials: G
authors.lastname: Carrier
authors.forename: L
authors.initials: L
authors.lastname: Normandin
authors.forename: G
authors.initials: G
authors.lastname: Kennedy
authors.forename: R F
authors.initials: RF
authors.lastname: Butterworth
authors.forename: A
authors.initials: A
authors.lastname: Hazell
authors.forename: G
authors.initials: G
authors.lastname: Therrien
authors.forename: D
authors.initials: D
authors.lastname: Mergler
authors.forename: S
authors.initials: S
authors.lastname: Philippe
authors.forename: J
authors.initials: J
authors.lastname: Zayed
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000473:pathology; D002940:Circadian Rhythm / Q000187:drug effects; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000473:pathology* / Q000523:psychology; D009942:Organometallic Compounds / Q000378:metabolism* / Q000633:toxicity*; D010316:Particle Size; D010865:Pilot Projects; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009942:Organometallic Compounds; D008345:Manganese; C406182:manganese phosphate