title: Mancozeb, a fungicide routinely used in agriculture, worsens nonalcoholic fatty liver disease in the human HepG2 cell model.
abstract: Mancozeb, a manganese/zinc ethylene-bis-dithiocarbamate, is a fungicide routinely used in pest control programs. However, it has been found to have deleterious effects on human health and on the environment. Indeed, its massive use has raised the issue of possible health risks for agrarian communities; the molecule can also reach human cells via the food chain and alter metabolism, endocrine activity and cell survival. In particular, mancozeb induces many toxic effects on hepatic cell metabolism. For this reason, we investigated its effect in an in vitro model of hepatic damage, namely fatty acid-induced nonalcoholic fatty liver disease in the HepG2 cell line. We found that the hepatic toxicity of the fungicide exacerbated fatty acid-induced steatosis, as manifested by an increase in intracellular lipid droplet accumulation. Furthermore, mancozeb altered cell metabolism and induced cell death through upregulation of lactate dehydrogenase and cytochrome c, respectively, in dose-dependent manners. Therefore, mancozeb may play an important role in the pathogenesis and progression of chronic disease in humans and represents a danger for human health in high doses.
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology medical histology and Molecular Biologiy, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy.
authors.forename: Anna Virginia Adriana
authors.initials: AV
authors.lastname: Pirozzi
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology medical histology and Molecular Biologiy, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Stellavato
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology medical histology and Molecular Biologiy, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: La Gatta
authors.affiliation: Department of Experimental Medicine, Section of Hygiene, Occupational Medicine and Forensic Medicine, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Lamberti
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology medical histology and Molecular Biologiy, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy. Electronic address: chiara.schiraldi@unina2.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Schiraldi
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005659:Fungicides, Industrial / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008344:Maneb / Q000633:toxicity*; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced*; D015038:Zineb / Q000633:toxicity*
chemical_list: D005659:Fungicides, Industrial; D008344:Maneb; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; C013099:mancozeb; D015038:Zineb
keywords: Fungicide hepatoxicity; HepG2; Mancozeb; NAFLD