Arsenic hepatotoxicity

Coke oven emissions are complex mixtures of hydrocarbons, including benzene and polynuclear aromatic compounds heavy metals including arsenic, beryllium, and cadmium and other particulates and vapors. In a study of coking workers in Taiwan, it was found that liver function profiles were altered by exposures to coke oven emissions and that exposure to even low levels of these emissions was hepatotoxic. The authors of the study suggest that the adverse hepatotoxic effects are caused by a mixture of chemicals rather than by any one identifiable speciesJ36 ... 

Park BK, Kitteringham NR, Maggs JL, Pirmohamed M, Williams DP (2005) The role of metabolic activation in drug-induced hepatotoxicity. Annu Rev Pharmacol Toxicol 45 177-202 Pi J, Qu W, Reece JM, Kumagai Y, Waalkes MP (2003) Transcription factor Nrf2 activation by inorganic arsenic in cultured keiatinocytes involvement of hydrogen peroxide. Exp Cell Res... 

Animal models, rodents in particular, are used to predict hepatotoxicity. However, due to differences in metabolism between species, conventional animal models cannot be as accurately predictive of human hepatotoxicity as primary human hepatocytes. For example, rodents are much more effective at detoxifying arsenic than humans (Wang et al., 2006), and animal testing of fialuridine was not predictive of severe hepatotoxicity in humans leading to five deaths during clinical trials (McKenzie et al., 1995). Despite these limitations, the use of conventional animals during safety assessment is commonplace. 

Fibrosis usually results from chronic inflammation, which can be the result of continuous exposure to a variety of hepatotoxic chemicals, such as organic arsenicals, vinyl chloride, or high doses of vitamin A (Zimmerman, 1999), chronic ethanol ingestion, and NAFLD. Fibrosis usually occurs around the portal area, in the space of Disse, and around the central veins. This results in loss of liver architecture and function. The hepatocytes are replaced with fibrous material, and thus there is hepatocyte loss. Periportal fibrosis may lead to portal hypertension. 

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