Microplastics Combined with MEHP Induced Mitochondrial Damage and Oxidative Stress via Inhibiting SIRT3/SOD2 in Hepatocytes.

Microplastics (MPs) are usually co-exposed with a variety of plastic-related products. This co-exposed is harmful to human health. Mono-2-ethylhexyl phthalate (MEHP) is a primary metabolite of di-2-ethylhexyl phthalate (DEHP), a common plasticizer. Once entering into the body, MPs and MEHP accumulate in the liver. Therefore, it is important to study the toxic effects of the co-exposed of MPs and MEHP on the liver and explore the potential mechanisms. In this study, HepG2 cells were treated with polystyrene microplastics (PS-MPs), MEHP, or PS-MPs combined with MEHP. The cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and protein expression of COXI, COXIII, SIRT3 and SOD2 were measured. The results showed that PS-MPs or MEHP exposure increased ROS generation and decreased MMP. PS-MPs exposure alone reduced protein expression of COXI and COXIII. These harmful effects were more pronounced when combined exposure, indicated a synergistic effect. Further molecular mechanism study exhibited that PS-MPs treatment down-regulated the protein expression of SIRT3 and SOD2. MEHP treatment down-regulated the protein expression of SIRT3. The combined exposure of PS-MPs and MEHP synergistically down-regulated the protein expression of SIRT3 and SOD2. In summary, the combined exposure of PS-MPs and MEHP resulted in oxidative stress and mitochondrial damage in HepG2 cells, and the underlying molecular mechanism is related to the inhibition of the SIRT3/SOD2 signaling pathway. [ABSTRACT FROM AUTHOR]