The role of the enzymatic antioxidant system in cylindrospermopsin-induced toxicity in human lymphocytes

- CYN rapidly increases ROS generation in human lymphocytes.
- CYN can alter the balance of enzymatic antioxidant status.
- CYN affects the status of SOD, CAT and GPx and increases lipid peroxidation.
- ROS and antioxidant imbalance are likely behind CYN-induced cellular dysfunction.

Cylindrospermopsin (CYN) is known to induce cytotoxic effects in eukaryotic cells although the exact mechanism underlying these alterations is not fully explained. Given that CYN was previously found to decrease the proliferation of human lymphocytes through DNA damage and cell cycle arrest followed by an increase in the apoptotic rate, the present study evaluated the possible involvement of reactive oxygen species (ROS) and oxidative stress in these cytopathic responses. The status of enzymatic antioxidants: superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as level of lipid peroxidation (LO) under CYN influence in human lymphocytes were also studied. It was found that CYN exposure (0.01-1.0 μg/ml) induces a concentration-dependent increase in H2O2 content within a time as short as 0.5 h, reaching its maximum level after 3 and 6 h. The highest H2O2 content was accompanied by a significant decrease of SOD and CAT activity and an elevated level of GPx. Moreover, CYN treatment resulted in a detectable increase in LO. We conclude that ROS and the products of LO play an essential role in CYN-induced toxicity in human lymphocytes. Our study helps to elucidate the sequence of events caused by CYN in eukaryotic cells and explain the background for previously observed cytopathic responses.