Altered generation pattern of reactive oxygen species triggering DNA and plasma membrane damages to human liver cells treated with arsenite.

Human exposure to arsenic via drinking water is one of globally concerned health issues. Oxidative stress is regarded as the denominator of arsenic-inducing toxicities. Therefore, to identify intracellular sources of reactive oxygen species (ROS) could be essential for addressing the detrimental effects of arsenite (iAs). In this study, the contributions of different pathways to ROS formation in iAs-treated human normal liver (L-02) cells were quantitatively assessed, and then concomitant oxidative impairs were evaluated using metabolomics and lipidomics approaches. Following iAs treatment, NADPH oxidase (NOX) activity and expression levels of p47 and p67 were upregulated, and NOX-derived ROS contributed to almost 60.0 % of the total ROS. Moreover, iAs also induced mitochondrial superoxide anion and impaired mitochondrial respiratory function of L-02 cells with a decreasing ATP production. The inhibition of NOX activity significantly rescued mitochondrial membrane potential in iAs-treated L-02 cells. Purine and glycerophospholipids metabolisms in L-02 cells were disrupted by iAs, which might be used to represent DNA and plasma membrane damages, respectively. Our study supported that NOX could be the primary pathway of ROS overproduction and revealed the potential mechanisms of iAs toxicity related to oxidative stress.