Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells.
Myclobutanil is a conazole class fungicide widely used as an agrichemical. It is approved for use on fruit, vegetables and seed commodities in the EU and elsewhere to control fungi such as Ascomycetes, Fungi Imperfecti and, Basidiomycetes. Its widespread use has raised the issue of possible health risks for agrarian communities and the general population, which can be exposed to residues present in food and drinking water. The toxicities identified include adverse effects on liver and kidney and on the development of male reproductive organs. Since the liver is the first-line organ in the defense against xenobiotics, toxic effects on hepatic metabolism cause degeneration, necrosis, and tissue hypertrophy. Therefore, we investigated myclobutanil's effects on the human liver cell line HepG2. We found that myclobutanil increases the amount of fatty acids in these hepatic cells, as evaluated with Oil Red O staining, and progressively reduces cell viability from 1ppm to 500ppm. Analysis of biomarkers such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at low doses. Therefore, myclobutanil may play an important role in the pathogenesis and progression of chronic hepatocellular diseases in humans.
Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy.
Antonietta
A
Stellavato
Department of Experimental Medicine, Section of Hygiene, Occupational Medicine and Forensic Medicine, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy. Electronic address: monica.lamberti@unina2.it.
Monica
M
Lamberti
Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy.
Anna Virginia Adriana
AVA
Pirozzi
Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy.
Francesca
F
de Novellis
Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Via de Crecchio 7, 80131 Naples, Italy.
Chiara
C
Schiraldi
D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005659:Fungicides, Industrial / Q000633:toxicity*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009570:Nitriles / Q000633:toxicity*; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced* / Q000473:pathology*; D014230:Triazoles / Q000633:toxicity*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494772:BAK1 protein, human; D005227:Fatty Acids; D005659:Fungicides, Industrial; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009570:Nitriles; D014230:Triazoles; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; D045304:Cytochromes c; C446685:systhane; D007770:L-Lactate Dehydrogenase
Conazole fungicide; HepG2 cells; Hepatoxicity; Myclobutanil; Nonalcoholic fatty liver disease