The Toxic Effect Of Ethephon On Mice Liver

Objective:The aim of the current study was to investigate the hepatotoxicity of ethephon and its possible toxicity mechanism,using C57 mice as the research object so as to lay a foundation for the discussion of the hepatotoxicity mechanism of ethephon and provide a basis for the safe and standardized application of ethephon in agriculture.Method:80 healthy C57 mice（40males and 40 females）were randomly divided into three experimental groups and one control group,each consisting of 10 males and 10 females,the experimental groups were given ethephon everyday at the dose of 1/10LD50(429.0mg·kg^-1)、1/20LD₅₀(214.5 mg·kg^-1)、1/40LD₅₀(107.2 mg·kg^-1)respectively by gavage.After 20 and 40 days,the animals of four groups were sacrificed.The liver of mice was dissected to prepare liver tissue homogenate,and the indexes of oxidative damage of T-SOD,GSH-Px,CAT and MDA in liver were determined.The activity indexes of NO and NOS in liver and metabolic enzyme activity indexes of ALT,AST,LDH,LAP,MAO,TBIL in liver tissue were determined.Energy metabolism enzymes Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase were also measured.The single-cell suspension of liver was prepared to measure the apoptosis of liver cells.Result:1.Results of body weight and organ coefficientAfter 20 days of ETH administration,body weight of male rats in 214.5 mg·kg^-1ETH group was decreased compared with other groups,liver organ coefficient was higher than other groups（P<0.05）.After 40 days of ETH administration,the body weight of female rats in 429.0 mg·kg^-1 ETH group was lower than that in other groups（P<0.05）.2.Results of indexes of oxidative damage in mice liverAfter 20 days of ETH administration,the level of T-SOD in each dose group and the MDA content was higher than that in control group（P<0.05）.For about the female mice,the CAT and GSH-Px activities in all ETH groups was decreased compared with control group（P<0.05）.The GSH-Px activity of 107.2 mg·kg^-1 and 429.0 mg·kg^-1 ETH groups were significantly different from the control group（P<0.05）.After 40 days of gavage,levels of T-SOD and CAT activity in 429.0 mg·kg^-1 ETH group were lower than those in control group（P<0.05）.Compared with control group,GSH-Px activity in 214.5 mg·kg^-1 and 429.0 mg·kg^-1 ETH groups were decreased（P<0.05）;MDA content in 429.0 mg·kg^-1 ETH group was higher than that in other groups（P<0.05）.The level of T-SOD in 107.2 mg·kg^-1 and 214.5 mg·kg^-1ETH groups and the content of MDA in 429.0 mg·kg^-1 ETH groups were higher than those in control group（P<0.05）.CAT activity in 214.5 mg·kg^-1ETH group and GSH-Px in 429.0 mg·kg^-1ETH group were lower than those in control group（P<0.05）.3.Results of NO and NOS in mice liverAfter 20 days of ETH administration,the content of NO in both male and female rats was higher than that in control group（P<0.05）.The NOS activity of male mice in107.2 mg·kg^-1 ETH group was lower than control group（P<0.05）.The NOS level in214.5 mg·kg^-1 and 429.0 mg·kg^-1 ETH groups was higher than that in control group（P<0.05）.NO level and NOS activity in 214.5 mg·kg^-1 and 429.0 mg·kg^-1 ETH groups were higher than those in control group（P<0.05）The NOS and NO activities in 214.5 mg·kg^-1 and 429.0 mg·kg^-1 ETH groups were higher than those in control group（P<0.05）.4.Results of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase in mice liverAfter 20 days of ETH administration,levels of Na⁺-K⁺-ATPase in 214.5 mg·kg^-1and 429.0 mg·kg^-1 ETH groups and Ca²⁺-Mg²⁺-ATPase in 429.0 mg·kg^-1 ETH groups were lower than those in control group（P<0.05）.The activities of Na⁺-K⁺-ATPase in107.2 mg·kg^-1 and 214.5 mg·kg^-1 ETH groups were lower than that in control group（P<0.05）.Na⁺-K⁺-ATPase activity in 429.0 mg·kg^-1 ETH group,Ca²⁺-Mg²⁺-ATPase activity in 214.5 mg·kg^-1 ETH group and 429.0 mg·kg^-1 ETH group were higher than those in control group（P<0.05）.After 40 days of ETH administration,levels of Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase in 107.2 mg·kg^-1 and 214.5 mg·kg^-1 groups were lower than those in control group（P<0.05）.Activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase were increased in female rats（P<0.05）.5.Results of metabolic enzymes in mice liver tissueAfter 20 days of ETH administration,the levels of ALT,AST and LDH in 107.2mg·kg^-1 and 429.0 mg·kg^-1ETH groups were higher than those in control group（P<0.05）.The ALT level in 429.0 mg·kg^-1 ETH group was lower than that in other groups（P<0.05）.Levels of AST and LDH in each group were decreased compared with control group（P<0.05）.After 40 days of ETH administration,the levels of ALT and AST in 214.5 mg·kg^-1 and 429.0 mg·kg^-1 ETH groups and LDH in 214.5 mg·kg^-1 and 429.0 mg·kg^-1ETH groups were lower than those in control group（P<0.05）.The levels of ALT,AST and LDH in 429.0 mg·kg^-1 ETH group,107.2 mg·kg^-1 ETH group and 429.0 mg·kg^-1ETH group were lower than those in control group（P<0.05）.After 20 days of gavage,level of LAP in 429.0 mg·kg^-1 ETH group was lower than that in other groups（P<0.05）.Compared with control group,MAO and TBIL activities in each group were increased（P<0.05）.Both MAO level,TBIL level in 214.5 mg·kg^-1and 429.0 mg·kg^-1ETH group were lower than those in control group（P<0.05）.After 40 days of ETH administration,LAP level of male rats in 107.2 mg·kg^-1 and429.0 mg·kg^-1 ETH group was lower than that in control group（P<0.05）.The levels of MAO and TBIL in each dose group were higher than those in control group（P<0.05）.The levels of LAP and TBIL in each dose group were lower than those in control group（P<0.05）.The MAO level in 107.2 mg·kg^-1 and 214.5 mg·kg^-1 ETH groups were higher than that in control group（P<0.05）.6.Results of apoptosis of hepatocytes in each groupAfter 40 days of administration,the apoptosis rate of hepatocytes in ethephon groups in both male mice and female mice were higher than that in control group（P<0.05）.Conclusion:1.ETH can interfere with the lipid peroxidation process of mouse liver,leading to changes in the activities of T-SOD,CAT,GSH-Px and MDA in liver tissues.2.ETH can affect the activity of cytokines related enzymes in mouse liver,resulting in the increase of NO and NOS activity in liver tissue.3.ETH exposure can cause energy metabolism disorder of liver cells,reduce the activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase in male rat liver tissue,and increase the activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase in female rat liver tissue.4.ETH exposure can interfere with the metabolic ability of mouse liver,resulting in changes in the activities of ALT,AST and LDH,and fluctuations in the activities of MAO,LAP and TBIL.5.ETH can increase the apoptosis rate of hepatocytes in mice.