Effects of Cadmium and/or Lead on Autophagy and Liver Injury in Rats.

Exposure to cadmium (Cd) and lead (Pb) can induce liver damage. However, the effects of the combined exposure to Cd and Pb on liver function have not been fully clarified. In the present study, we investigated the liver function in rats co-exposed to Cd and Pb. A total of 24 female SD rats were divided into 4 groups as follows: control group (DDW), Cd group (50 mg/l Cd), Pb group (300 mg/l Pb), Pb + Cd group (300 mg/l + 50 mg/l Cd). Following 12 weeks of continuous exposure, the results showed a large accumulation of Cd and Pb in the liver. The Liver weight and Liver coefficient were decreased, as well as liver structure and function was destroyed. In addition, Pb + Cd group exhibited additional pathological alterations. Moreover, the indices of oxidative stress and related trace elements were detected following treatment. The results showed that the single treatment of Pb or Cd and the combined Cd and Pb treatment could upregulate the contents of antioxidant enzymes and related trace elements. We further examined the expression levels of autophagy-related proteins and mRNAs, and we found that the single treatment of Pb or Cd and the combined Cd and Pb treatment could upregulate the expression of levels of autophagy-related proteins and mRNAs (Atg5, Atg7, Beclin-1, p62, and LC3). Transmission electron microscopy revealed the presence of autophagosomes in the exposed groups. All the results indicated that Cd and Pb may affect the level of oxidative stress and autophagy in hepatocytes, whereas the combination of Cd and Pb showed a tendency of escalation compared with the single treatment group.