title: Maneb causes pro-oxidant effects in the hippocampus of Nrf2 knockout mice.
abstract: The effects of maneb were investigated in C57BL/6 Nrf2 wildtype and knockout mice. Treated KO mice showed significant weight loss as compared to WT counterparts. ICPAAS analysis demonstrated a significant increase in manganese concentration in the tissues of treated KO mice as compared to WT. Biochemical analysis revealed significant decreases of antioxidants including glutathione, glutathione reductase and heme oxygenase-1. Levels of TBARS were significantly increased in hippocampal tissue in Nrf2 KO mice at the 30 and 60mg doses. qPCR demonstrated that the only gene mediated by the Nrf2 transcription pathway that was significantly modulated by at least 1.5 fold was glutathione peroxidase 4. GPX4 was significantly upregulated in Nrf2 WT mice treated with 30mg/kg maneb and significantly downregulated in Nrf2 KO mice treated with the same dose. Microscopy revealed neuronal pyknosis and eosinophilia of the cytoplasm in the hippocampi of both WT and KO animals treated with 60mg/kg maneb.
authors.affiliation: Department of Pharmaceutical Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, United States.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Kurzatkowski
authors.affiliation: Department of Pharmaceutical Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, United States. Electronic address: trombetl@stjohns.edu.
authors.forename: Louis D
authors.initials: LD
authors.lastname: Trombetta
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005659:Fungicides, Industrial / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008344:Maneb / Q000633:toxicity*; D008345:Manganese / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency* / Q000235:genetics; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D005659:Fungicides, Industrial; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D008344:Maneb; D008345:Manganese; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D005980:Glutathione Reductase; D005978:Glutathione
keywords: Fungicide; Hippocampus; Maneb; Manganese; Nrf2; Oxidative stress; Thyroid