The Establishment Of Cirrhosis Model In New Zealand Rabbits By Carbon Tetrachloride And The Observation Of Acute Liver Injury By Aflatoxin B1 In This Model

Background We found individual variations of liver injury relevant to aflatoxin B1(AFB1)exposure in epidemiology study,which raises the hypothesis that underlying liver diseases might interfere AFB1 metabolism in vivo and detoxification,contributing to personal susceptibility to hepatocarcinogenesis.Therefore studying the AFB1-relevant liver damage in hepatitis virus(HV)infectants might help exploring of the synergistic effect, if any,of HV and chemical carcinogen in inducing cancer.Aims The purpose of this study is to establish a relatively simple yet stable cirrhotic model in New Zealand rabbits with Carbon Tetrachloride (CCl₄)treatment.We observed the acute effect in liver by additional AFB1 treatment in this model.This study might provide animal tool for etiology study on primary hepatocellular carcinoma.Methods Stage-1:Twenty-four male New Zealand white rabbits were randomized into A,B,C and D groups,given placebo,low,medium and high dosages of CCl₄,respectively.The levels of BW(body weigh),TP(total protein),Alb(albumin),Glo(globulin),ALT(alanine aminotransferase), AST(aspartate transaminas),G-GT(γ-glutamyltransferase),WBC(white blood cell),RBC(red blood cell),HGB(hemoglobin)and PLT(platelet) in each group were recorded.Liver biopsy were conducted every two weeks in a randomly manner.At stage-2,CCl₄ treatment was stopped when liver biopsy revealed pathological cirrhosis.And the above indices were continually recorded for 8 weeks.Meanwhile,biopsy was conducted to monitor the stability of the liver cirrhosis.At the third stage,the survival New Zealand rabbits were subjected into two groups,one of them were given 0.5 mg / kg of AFB1,I.P. and sampled for liver function and hemogram indices quantification.Results Three New Zealand rabbits in Group C died in the 2^nd- 3^rdweek, five rabbits in Group D died in the 10^thweek.The liver pathology for cirrhosis revealed that all animals in group-A were staged SO,three in group-B were S4 and the other two were S3.At the second stage,biopsy showed that liver fibrosis of 5 New Zealand rabbit in the Group B improved significantly in the third week (P＜0.05).At the third stage,the levels of TP,Alb,Glo,ALT,AST, G-GT,WBC,RBC,HGB and PLT in rabbits two hours after AFB1 injection were similar to that in the controls(P＞0.05)Conclusion Pathological cirrhosis appeared in male New Zealand white rabbits receiving subcutaneous injection of 0.3 ml / kg CC14 dissolved in olive oil(1:1 ratio)once every three days for ten weeks.The fibrosis improved in less than three weeks after the withdrawal ofCCl₄,and both liver function and hemogram indices recovered to normal levels,suggesting that a sustained treatment of CCl₄ is necessary to maintain the cirrhotic model.Intraperitoneal injection of 0.5 mg / kg of AFB1 had little influence on the levels of liver function and hemogram indices within two hours.