Cadmium (Cd) is an environmental heavy metal with long biological half-time and adverse health effects. The long-term toxicity of Cd at low levels remains to be elucidated. Here, we investigated the impact of dietary Cd intake at environmental doses in the full disease cycle from liver injury, fibrosis, inflammation to cancer progression in mouse models and in vitro. We found that chronic low-dose Cd exposure promoted the hepatotoxicity and hepato-pathogenesis in normal and CCl4 mouse models. Cd enhanced liver injury and accelerated liver fibrosis, a key risk factor for cirrhosis and liver cancer, featured as up-regulation of fibrosis-related markers (TGF-β1, collagen-1, and TIMP1) and activation of hepatic stellate cells. Consistently, Cd increased the inflammation and the infiltration of macrophages and dendritic cells in liver. At late stage, the angiogenetic factors, VEGF and CD34, were elevated, indicating abnormal angiogenesis. At the end of treatment, Cd promoted CCl4-induced...

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