Optimization of an experimental model of hepatic fibrosis induced by carbon tetrachloride

Objective To optimize the liver fibrotic animal model induced by carbon tetrachloride (CCl4).Methods The optimization of the liver fibrotic animal model involved doses of CCl4,routes of CCl4 administration and animal species.To find the suitable dose of CCl4 for modeling,KM mice were injected intraperitoneally with CCl4 at the dose of 0.5,0.75,1 ml/kg body weight,twice a week,for a total of 8 weeks.From the beginning of the 9th week CCl4 injection was stopped,but the test lasted until the 12th week.To optimize the routes of CCl4 administration,ICR mice were treated with CCl4 intraperitoneally or intragastrically,twice a week,totally 12 weeks.To compare mice and rats for modeling,we administrated CCl4 to ICR mice or SD rats intragastrically,twice a week,totally 12 weeks.Results After 8 weeks of CCl4 injection,in the 10th week there were collagen fibers limited in portal areas of the 0.5 ml/kg CCl4 group,fibrous septum was formed in the 0.75 ml/kg CCl4 group and early cirrhosis in the 1 ml/kg CCl4 group,suggesting that the appropriate CCl4 dose was 1 ml/kg.Although intraperitoneal injection and intragastric administration both induced apparent fibrosis,the death rate after intraperitoneal injection was up to 80%,vs 10% or below after intragastric administration which proved to be a better administration.Trends of liver fibrotic indicators of rats and mice were comparable and changes of rats were more evident.Conclusion To establish liver fibrosis induced by CCl4,1 ml/kg CCl4 and intragastric administration should be adopted and animal species should be chosen according to the purposes.