title: The effect of high dose oral manganese exposure on copper, iron and zinc levels in rats.
abstract: Manganese is an essential dietary nutrient and trace element with important roles in mammalian development, metabolism, and antioxidant defense. In healthy individuals, gastrointestinal absorption and hepatobiliary excretion are tightly regulated to maintain systemic manganese concentrations at physiologic levels. Interactions of manganese with other essential metals following high dose ingestion are incompletely understood. We previously reported that gavage manganese exposure in rats resulted in higher tissue manganese concentrations when compared with equivalent dietary or drinking water manganese exposures. In this study, we performed follow-up evaluations to determine whether oral manganese exposure perturbs iron, copper, or zinc tissue concentrations. Rats were exposed to a control diet with 10 ppm manganese or dietary, drinking water, or gavage exposure to approximately 11.1 mg manganese/kg body weight/day for 7 or 61 exposure days. While manganese exposure affected levels of all metals, particularly in the frontal cortex and liver, copper levels were most prominently affected. This result suggests an under-appreciated effect of manganese exposure on copper homeostasis which may contribute to our understanding of the pathophysiology of manganese toxicity.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, 02912, USA.
authors.forename: Courtney J
authors.initials: CJ
authors.lastname: Mercadante
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, 02912, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Herrera
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, 02912, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pettiglio
authors.affiliation: College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27607, USA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Foster
authors.affiliation: College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27607, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Johnson
authors.affiliation: College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27607, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Dorman
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, 02912, USA. thomas_bartnikas@brown.edu.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Bartnikas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003300:Copper / Q000378:metabolism*; D004032:Diet; D006706:Homeostasis / Q000187:drug effects; D007501:Iron / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000008:administration & dosage* / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D015032:Zinc / Q000378:metabolism*
chemical_list: D008345:Manganese; D003300:Copper; D007501:Iron; D015032:Zinc
keywords: Copper; Exposure; Iron; Manganese; Zinc