Question
Schistosoma mansoni infection induces oxidative stress in the liver, which so far presumably is caused by cells of the immune system. During co-infections with hepatitis B and C virus there is an increased risk for cancer development. SEA (Soluble Egg Antigen) isolated from S. mansoni eggs, activates carcinogenesis associated JNK/STAT3 pathways. With in vivo and in vitro studies, we aimed to analyze whether S. mansoni-induced oxidative stress is able to induce DNA damage and thus increase the risk for mutagenesis.
Methods Hamster livers of three different experimental groups (not infected, or infected with a single or both genders of S. mansoni) were used for western blotting, malondialdehyde (MDA) assay and catalase activity analysis. In cell culture experiments with HepG2 cells, we used SEA (Soluble Egg Antigen) to stimulate the cells as well as reduced glutathione (GSH) to prevent oxidative stress. Analyses have been performed by western blot, MDA assay and Comet assay.
Results In HepG2 cells SEA induced DNA damage. We show that GSH prevents oxidative stress and thus normalizes SEA-induced DNA damage. Comparing the oxidative stress levels, SEA-treated HepG2 cells and S. mansoni-infected hamsters show higher levels of the oxidative stress marker MDA than the control groups. The DNA repair mechanism protein p-H2AX is activated in SEA-stimulated cells and S. mansoni-infected hamsters. SEA-induced activation of JNK/STAT3 pathways and p-H2AX are normalized in cell culture experiments by simultaneous GSH-treatment.
Conclusions
S. mansoni induces hepatic oxidative stress in vivo and in vitro. Oxidative damage and consequently DNA damage in hepatocytes is caused by S. mansoni even during a lack of cells of the immune system. This implicates that the oxidative stress is not only caused by cells of the immune system, but additionally SEA itself causes hepatic oxidative stress. GSH is able to prevent SEA-treated cells from DNA damage and carcinogenesis-associated pathway activation.
