Therapeutic Effect Of Compound Embryonic Bovine Liver Extract On Nonalcoholic Fatty Liver Disease In Rat

PurposeNonalcoholic fatty liver disease (NAFLD) has emerged as one of the most common chronic liver diseases over the past decade. It consists of a spectrum of liver disease, ranging from simple steatosis to steatohepatitis, cirrhosis, liver failure, and hepatocellular carcinoma. NAFLD is strongly associated with obesity, type 2 diabetes and hyperdyslipidemia, which are the main features of the recently characterized metabolic syndrome. To date, no single therapy has been approved for treating NAFLD, but a growing consensus suggests that initial management must be focused on lifestyle modification and the reversal of conditions associated with NAFLD. Several proposed agents are under evaluation currently, each targeting a different step in the pathogenesis of the development of hepatic steatosis or progression to steatohepatitis. The proper dosing, duration of the treatment, safety, and tolerability of these treatment remain under investigation. Compound embryonic bovine liver extract is a newly development agent that mainly consists with embryonic bovine liver extract, vitamin B₁₂ and inositol. Regulatory roles of this agent on glucose and lipid metabolism have been observed in recent studies. However, whether this agent is suitable for the treatment of NAFLD remains unclear. In this study, we established a rat model of NAFLD using high-fat diet; potential therapeutic effect and mechanism of compound embryonic bovine liver extract on NAFLD were investigated.MethodsMale Sprague-Dawley rats were randomly divided into five groups: control group, model group, and 3 different therapy groups. Control group received a general diet, while model group and 3 different therapy groups received a high-fat diet. The therapy of compound embryonic bovine liver extract started at the 9^th week and lasted for 8 weeks. The dose for high, median, low-dose therapy group was 40, 24, 15 mg/kg/d, respectively. Liver species and serum samples were obtained at the end of study. The samples were used for histological examination and serum biochemical value analyses. The change of body weight, hepatic wet weight and hepatic index of the rats in different groups were also recorded.Results1. Histological analysisSevere hepatic steatosis and inflammatory infiltration were observed in the livers of model group after 16-week of high-fat diet, which mimic main features of human NASH. The degree of steatosis and inflammatory infiltration were significantly ameliorated by the therapy of compound embryonic bovine liver extract. The amelioration was the most obviously in the rats received high-dose compound embryonic bovine liver extract.2. Indexes of overweight and hepatomegaliaThe body weight was gradually increased in the rats fed by high-fat diet, whereas the increase was significantly prevented by high-dose treatment of compound embryonic bovine liver extract. Hepatic wet weight and hepatic index were also significantly reduced by the therapy. 3. Biochemical valuesSerum level of ALT, AST, ALP, TC, FBG and total bile acids was significantly increased in the rats fed by high-fat die when compared with the control group, whereas serum level of TG was significantly decreased. When compared with the model group, serum FBG level was significantly decreased by the therapy of compound embryonic bovine liver extract.4. Serum leptin levelSerum leptin level was greatly increased in the rats of model group after 16-week of high-fat diet, whereas the level was significantly decreased by the therapy of compound embryonic bovine liver extract.Conclusion:1. Compound embryonic bovine liver extract is effective to ameliorate hepatic steatosis and inflammatory infiltration in the rat model of NAFLD induced by high-fat diet, and the therapeutic effect was dose-dependent.2. The therapeutic mechanism of compound embryonic bovine liver extract on NAFLD is probably associated with the regulatory role on serum glucose metabolism.3. Decreasing serum leptin level may be another mechanism for the therapeutic effect of compound embryonic bovine liver extract on NAFLD.