The Study Of Hepatotoxicity And Mechanism Of Mitochondrial Pathway Damage By Dioscorea Bulbifera L.in Mice

Dioscorea bulbifera L.is the dry tuber of Dioscorea bulbifera and has complex chemical composition mainly containing steroidal saponins,flavonoids,two lactones,phenolic acids,tannins,sugars,starch and other ingredients,in addition Dioscorea bulbifera L.also contains manganese,iron,zinc,iodine and other trace elements,and research shows that the Dioscorea bulbifera L.has a therapeutic effect to thyroid diseases,cancer,psoriasis.In recent years,in vivo toxicity of Dioscorea bulbifera L.has repeatedly reported,indicate that clinical use will cause hepatotoxicity,but the mechanism of hepatic injury caused by Dioscorea bulbifera L.is unclear.Objective:The aim of this research is to discuss the hepatotoxicity of water extraction of Dioscorea bulbifera L.?WED?in mice and discuss the role of mitochondrial in liver injury mechanism in by WED.Methods:the mice were given WED in different concentrations,the male ICR mice were divided into four groups,normal control?water?,low dose group(19.6g·kg^-1),moderate dose group(28g·kg^-1),high dose group(40g·kg^-1)to ig for 14 d,21d and 28 d.later,we recorded the body weight,calculate the liver indexes,detecte serum alkaline phosphatase?ALP?,alanine aminotransferase?ALT?,aspartate transaminase?AST?,to evaluate the the hepatotoxicity by WED.Detected the ROS,MDA and ATP levels,the activity of T-SOD in liver,the avtivity of Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase and Mn²⁺-SOD in liver mitochondrial,to infer the mechanism of mitochondria damage.Results:Compared with the normal control group,the mice were given the WED for 14 d,21 d and 28 d,the body weight of high dose group was significate decreased,p<0.05.The liver indexes of all dose groups were significant increased,p<0.05.In all dose groups,ALT,AST,ALP contents were significate difference,p<0.05.The ROS,MDA contents were significant increased,p<0.05.The ATP contents were significant decreased,p<0.05,the activity of T-SOD was significant increased,p<0.05 in all dose groups.The activity of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase wassignificantdecreased,p<0.01,theactivityofMn²⁺-SODwassignificant increased,p<0.05.Correlationanalysesbetweentheliverindexes,thecontentsof ALT,AST,ALP,ROS and MDA,the concentration and time has significant positive correlation,p<0.05.The body weight and the activity of Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase has significant negative correlation,p<0.05.Conclusion:The study show that WED could induce liver injury,and the mechanism related to weaken the synthesis of ATP and oxidative damage,decreased the activity of Na⁺-K⁺-ATPase?Ca²⁺-Mg²⁺-ATPase,destroyed the balance of inside and outside membrane of mitochondrial,and the damage was dependent with the concentration and time,prove the mitochondrial is an importent target of the liver injury by Dioscorea bulbifera L.