Silybin-phospholipid Complex Intervention Of Drug-induced Fatty Liver Caused By Amiodarone In Mice-An Experimental Study

Objective Establishing mice model of drug induced fatty liver by amiodarone(AMD), to evaluate the role of silybin- phospholipid complex on amiodarone induced fatty liver. To provide reference for clinical prevention and treatment of amiodarone induced liver injury. Methods Mice were given amiodarone with 80mg/kg、120mg/kg、150mg/kg by oral gavage,once a day, for seven days, to establish animal model of drug induced fatty liver. Through routing pathological staining(H&E)and oil red staining to clear appropriate concentration of amiodarone to induced fatty liver model in mice. Then,intervention therapy of silybin- phospholipid complex(50mg/kg) for drug induced fat liver tried at this optimal dose of amiodarone. To detect changes in lipid metabolism by serum alanine aminotransferase( ALT),aspartate aminotransferase(AST),H&E, oil red staining, electron microscopic analysis, RT-PCR. Result The liver tissue of mice have showed no obvious liver fatty degeneration for treatment group of amiodarone 80mg/kg, 120mg/kg;Obviously red fat droplet deposition by oil red staining can be seen in the group of amiodarone 150 mg/kg. H&E staining revealed microsteatosis within hepatic cells. The serum levels of ALT, AST, cholesterol(CHOL), high density lipoprotein(HDL) and triglycerides(TG). were no changes in the 150 mg /kg amiodarone treatment group and silibinin- phospholipid complex therapy group. The degree of fatty liver in Silybin- phospholipid complex treatment group is obviously reduced compared with amiodarone treatment group by H&E andoil red staining. Transmission electron microscopy showed liver cell structural integrity in the control group,no swelling and destruction for mitochondria structure.In model group, the liver cell nucleus pyknosis,mitochondrial swelling, structure damage, and autophagy lysosome. The intervention group compared with model group liver cell nuclei slightly damaged, but no pyknosis. The damage of mitochondria structure was slighter compared with model group. The mitochondrial structure and liver nuclei were slightly abnormal in intervention group compared with the control group. RT-PCR results showed, genes involved in fat catabolism:Acot1、Acot2、Cyp4a10(p<0.05)、Cyp4a14、Cyp2b10、ACOX(p<0.001)、Ehhadh(p<0.01),Compared with model group, control group expression was significantly increased, with statistical significance.Acot1, Cyp4a14 expression decreased by intervention group compared with the model group. The enzyme CPTI(p<0.05)、CPTII(p<0.001) which involved in mitochondrial beta oxidation,expression was significantly increased by model group compared with control group,with statistical significance. CPTI expression decreased by intervention group compared with the model group,with statistical significance(p<0.05).The fatty acid sensitive nuclear factor receptor HNF4 alpha, PPAR alpha, compared with model group, control group expression was significantly increased, with statistical significance(p<0.001).But expression was significantly increased by model group compared with control group,with statistical significance(p<0.05). Conclusion The model of fatty liver can be successfully established on gavage of amiodarone 150 mg /kg/d for 7 days in mice. Silybin- phospholipid complex can effectively reduce the amiodarone induced steatosis through alleviating mitochondrial damage. This may seem to imply that Silybin- phospholipid complex would be a potential therapy for drug induced fat liver by amiodarone.