Mitochondria-associated Endoplasmic Reticulum Membranes In Lycopene Against Dehp-Induced Liver Toxicity

Di(2-ethylhexyl)phthalate(DEHP)is an environmental endocrine disruptor that exists widely in the atmosphere,water,and soil,threatening human and animal health and affecting ecosystem balance.Lycopene(LYC)is one of the strongest antioxidants found in plants in nature and has multiple protective functions.The liver is one of the main target organs of toxic effects of DEHP,but the antagonistic effect of LYC on its liver toxicity is still unclear.In order to reveal the mechanism of LYC antagonizing DEHP-induced liver toxic effects,male ICR mice were used as test animal,DEHP or / and LYC were used for intragastric treatment,liver pathological observation was performed to determine liver function,nuclear receptors in tissues,CYP450 s,oxidation stress,mitochondrial dynamics related factors,endoplasmic reticulum stress pathway and mitochondrial-endoplasmic reticulum structure coupling related factors,etc.Our results show:(1)LYC can inhibit liver damage caused by DEHP,change blood biochemical indicators related to liver function(AST / ALT,TBIL,DBIL,and TP),and alleviate path ological histological damage(enlarged liver sinus space,blurred liver lobular structure,liver disorganized cells and nucleus dissolution)and ultrastructural damage(damaged mitochondrial structure,reduced crest,swollen endoplasmic reticulum,and membrane rupture).LYC activates the antioxidant enzyme system(SOD,GST,GSH-Px,CAT)of liver tissue,reduces the content of MDA and H2O2,and restores the ability of T-AOC in liver tissue.It shows the effect of antagonizing DEHP liver toxicity and DEHP-induced oxidative damage.(2)LYC reduces the expression of CYP450 subunits(CYP2E1,CYP1B1,CYP7B1,CYP2B1,CYP2C29,CYP2J5,CYP1A1,CYP2F2,CYP1A2)by initiating nuclear exogenous biological receptor(AHR,CAR,PXR)responses and further Antagonize the abnormal nuclear receptor response induced by DEHP.(3)LYC regulates the expression of mitochondrial fusion proteins(MFN2,MFN2,OPA1)and cleavage proteins(DRP1,FIS1,MFF),and regulates endoplasmic reticulum stress signal transduction factors(ATF6,ATF4,GRP78,GRP94,The expression of PERK,el F2?,CHOP)can inhibit the mitochondrial fusion / division steady state of DEHP exposure and destroy liver tissues,and can inhibit the endoplasmic reticulum stress of mouse liver induced by DEHP,thereby inhibiting liver cell damage.(4)LYC regulates the protein content of the physically connected factors(MFN2,GRP75)in the mitochondrial-endoplasmic reticulum structure coupling,thereby inhibiting the damage of the MAM structure of the mouse liver caused by DEHP exposure.To sum up,DEHP induces oxidative stress in the liver of mice and causes damage to liver mitochondria coupled to the endoplasmic reticulum and mitochondrial-endoplasmic reticulum structure.Lycopene antagonizes the oxidative stress of the liver caused by DEHP by initiating the nuclear receptor response,and exerts liver protection by regulating the physical connection of MAM structure,mitochondrial fusion and division,and endoplasmic reticulum stress.