Study On The Mechanism Of Lycopene Antagonist Against Atrazine-Induced Ferroptosis In Mice Liver

Atrazine?ATR?is currently the highest-selling herbicide in the world.Because of its stable nature and long half-life and serious pollution to the living environment,ATR has been listed as an environmental endocrine disruptor?EDC?by the World Health Organization.ATR can cause serious damage to the nervous system,immune system,endocrine system and reproductive system,threatening the health of organisms.Lycopene?LYC?is a natural and efficient antioxidant and free radical scavenger founded at present.It is widely found in mature red plant fruit and is known as“plant gold”.At present,the antagonistic mechanism of LYC against ATR-induced hepatotoxicity in mice is still in the preliminary stage,so this experiment took mice as the experimental model and was continuously exposed by intragastric administration for 21 days to explore the toxic effect of the observation of histomorphology and ultrastructure of mice liver,detection of liver function,detection of antioxidant capacity and oxidation products,detection of the expression of Nrf2 signal pathway,lipid metabolism pathway,system X_c^-/GPX4 pathway,ferritin and iron homeostasis related regulatory factors expression.To analyzed the mechanism of ATR induced ferroptosis in mice liver and the antagonistic effect of LYC on it.The results showed that:?1?LYC alleviated liver dysfunction?AST,ALT,ALP,ALB,TBIL,A/G?caused by ATR exposure in mice,as well as pathological changes such as hepatocyte steatosis,enlarged cell space,cell necrosis,and damaged mitochondrial structure.?2?LYC antagonized oxidative stress induced by ATR in mice liver,enhanced the activity of related antioxidant enzymes?CAT?GPX?GSH?SOD?T-AOC?in liver and reduced the accumulation of MDA?H₂O₂.LYC promoted the expression of Nrf2 and its downstream factor such as SOD?NQO1?HO-1?GCLC?GCLM?CAT GPX,and enhanced the antioxidant effect.?3?LYC inhibited lipid synthesis and accumulation in mice liver by reducing AA synthesis,down-regulating ACSL4 and PTGS2 expression.LYC attenuated liver ferroptosis?mitochondrial shrinkage,increased mitochondrial membrane density,and decreased nuclear heterochromatin distribution?caused by ATR exposure in mice,enhanced the negative regulation of ferroptosis by system X_c^-/GPX4 pathway by upregulating SLC7A11?SLC3A2 and GPX4 expression.By inhibiting TFR1 receptor expression,enhancing iron storage protein synthesis,regulating iron homeostasis and iron metabolism in mice liver,prevented excessive accumulation of iron in cells and accelerated ferroptosis.To sum up,ATR exposure can damage the structure and function of mice liver,cause oxidative damage of liver tissue,increase the accumulation of lipid peroxidation products,destroy intracellular iron homeostasis,and then induce ferroptosis.LYC can enhance the function of liver antioxidant system to remove lipid peroxidation products,resist oxidative stress,correct abnormal iron metabolism,restore liver structure and function,and antagonize ferroptosis in mice liver.