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.
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