Wang 2016b Toxicol Sci
| Wang B, Klaren WD, Wels BR, Simmons DL, Olivier AK, Wang K, Robertson LW, Ludewig G (2015) Dietary manganese modulates PCB126 toxicity, metal status, and MnSOD in the rat. Toxicol Sci 150:15-26. |
Wang B, Klaren WD, Wels BR, Simmons DL, Olivier AK, Wang K, Robertson LW, Ludewig G (2015) Toxicol Sci
Abstract: PCB126 (3,3',4,4',5-pentachlorobiphenyl) is a potent aryl hydrocarbon receptor agonist and induces oxidative stress. Because liver manganese (Mn) levels decrease in response to PCB126, a Mn dietary study was designed to investigate the role of Mn in PCB126 toxicity. Male Sprague Dawley rats received diets containing 0, 10, or 150 ppm added Mn for 3 weeks, followed by a single ip injection of corn oil or PCB126 (5 µmol/kg body weight). After 2 weeks, Mn, Cu, Zn, and Fe levels in the heart, liver, and liver mitochondria, and Mn-containing superoxide dismutase (MnSOD) and metallothionein mRNA, MnSOD protein, and MnSOD activity were determined. Mn levels in liver, heart, and liver mitochondria were strongly decreased by the Mn-deficient diet. Small effects on Fe levels and a stepwise increase in MnSOD activity with dietary Mn were also visible. PCB126 caused profound changes in Cu (up), Zn, Fe, and Mn (down) in liver, but not in heart, and differing effects (Cu, Zn, and Fe up, Mn down) in liver mitochondria. Liver MnSOD and metallothionein mRNA levels and MnSOD protein were increased but MnSOD activity was decreased by PCB126. PCB126-induced liver enlargement was dose-dependently reduced with increasing dietary Mn. These changes in metals homeostasis and MnSOD activity in liver but not heart may be a/the mechanism of PCB126 liver-specific toxicity. Specifically, transport of Fenton metals (Cu, Fe) into and Mn out of the mitochondria, a probable mechanism for lower MnSOD activity, may be a/the cause of PCB126-induced oxidative stress. The role of metallothioneins needs further evaluation. Dietary Mn slightly alleviated PCB126-induced toxicities.
© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: [email protected]. • Keywords: MnSOD, PCB126, Aryl hydrocarbon receptor, Diet, Manganese, Metallothionein
Labels: MiParea: Exercise physiology;nutrition;life style, Pharmacology;toxicology
Organism: Rat
Tissue;cell: Liver
Preparation: Isolated mitochondria
2016-04
