Chronic arsenic poisoning and Hepatotoxicity

Abstract

Arsenic (As) is a toxic and carcinogenic metalloid. Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Chronic arsenic poisoning, or arsenicosis, is typically defined by the classical skin manifestations, together with involvement of internal organs, such as liver injury, in the presence of known arsenic exposure. Probably, the most important concern with arsenic exposure is its carcinogenic potential. Epidemiologic studies have demonstrated an association between chronic arsenic exposure and cancer of the skin, lung, urinary bladder, and possibly liver, kidney, and prostate in humans. The epidemiological data for the skin, lung and urinary bladder are widely accepted as showing an etiological role for arsenic exposure, whereas other sites, such as liver, are considered more controversial. This article reevaluates epidemiology studies, rodent studies together with in vitro models, and focuses on the liver as a target organ of arsenic toxicity and carcinogenesis. Hepatocellular carcinoma and hepatic angiosarcoma, have been frequently associated with environmental or medicinal exposure to arsenicals. Hepatomegaly, hepatoportal sclerosis, fibrosis, and cirrhosis often occur after chronic arsenic exposure. There are a variety of potential mechanisms for arsenical-induced hepatocarcinogenesis, such as oxidative DNA damage, impaired DNA damage repair, acquired apoptotic tolerance, hyperproliferation, altered DNA methylation, and aberrant estrogen signaling. Some of these mechanisms may be liver specific/selective. Overall, accumulating evidence clearly indicates that the liver could be an important target of arsenic carcinogenesis.