Mancozeb, a fungicide routinely used in agriculture, worsens nonalcoholic fatty liver disease in the human HepG2 cell model

• In the present study, we found that the hepatic toxicity of Mancozeb, exacerbated fatty acid-induced steatosis.
• We found a strong reduction of cell viability, to below 50%, for mancozeb concentrations ranging 1–100 ppm. Indeed, 48 h of exposure to 100 ppm caused total cell death, as assessed by an MTT test.
• We found that the fungicide increased the amount of intracellular lipid droplets, with respect to fatty acid treatment alone, from 0.1 ppm to 100 ppm.
• The fungicide has an ability to modify the function of different enzymes, such LDH and cytochrome c, leading to cell death.

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