Liver and Cadmium Toxicity

Cadmium (Cd) is an important industrial and environmental toxicant with many industrial applications. Cd emissions to the atmospheric, aquatic, and terrestrial environment have increased during the last century. Since Cd is not degraded in the environment, the risk of human exposure is constantly increased due to Cd also enters to the food chain [1]. Humans are generally exposed to Cd by two main routes, inhalation and ingestion. Absorption of Cd by skin is relatively insignificant [2]. In humans and other mammals, Cd exposure can result in a variety of adverse effects, such as testicular damage, pulmonary edema, renal and hepatic dysfunction, osteomalacia, etc. In addition to the direct cytotoxic effects that could lead to apoptotic or necrotic event, Cd has been implicated in the development of cancer and it has been classified as a type I carcinogen by the International Agency for Cancer Research [3]. Emerging evidence suggests that Cd exposure affects Cytochrome P 450 1A1 (Cyp1A1). Cyp1A1 has been always associated with the transformation of pro-carcinogenic compounds to highly carcinogenic metabolites [4]. Chronic Cd intoxication results mainly in renal disease [5,6] but acute Cd exposure primarily results in liver accumulation and hepatocellular damage. After acute exposure to inorganic forms of Cd, the preponderance of the dose accumulates in the liver [7]. Cadmium retention is generally higher in women rather than men [8]. Gender differences in susceptibility, at lower exposure, are uncertain, but some data indicate that Cd has estrogenic effects and affects female offspring [8]. Humans are susceptible to Cd toxicity primarily through the ingestion of contaminated food or water and the inhalation of cigarette smoke. Today, nanotechnology with the development of Cd-containing nanoparticules, could be also a source of metal exposure [9]. Gastrointestinal ingestion of Cd through food or drinking water is the major route of intake for this metal in nonsmoking and non-occupationally exposed populations [10]. Cigarette smoke is the largest source of Cd exposure in general population. Each cigarette could contain up to 6.67 μg Cd, and 40-60% of it generally passes through the pulmonary epithelium into systemic circulation.