Induction of Acute Hepatic Failure by Carbon Tetrachloride in the NMRI Mouse Model

Backgroundand

Production of a model of hepatic failure is used to evaluate the effectiveness and safety of alternative methods of liver transplantation. This study aimed to determine the appropriate dosage of carbon tetrachloride (CCl4) to induce acute hepatic failure in NMRI mice.

In this study, at first, a mixture of CCl4 dissolved in olive oil was administered intraperitoneally to 5 groups of 6 mice. After 24 hours, serum level of liver enzymes and the status of liver tissue were evaluated. To investigate the survival of mice, CCl4 (at doses of 0.5, 1, 1.5, 2, and 2.5ml/kg.bw) was administered to 6 new groups of mice, and these animals were monitored for 4 days. To assess the effect of the toxin in the next days, the determined dose was administered to 24 new mice, and serum and histological evaluations were repeated.

The serum level of liver enzymes and the degree of hepatic lesions were significantly increased with increased dose of CCl4. Values more than 1ml/kg of CCl4 induced acute liver damage. Also, the value of 1ml/kg decreased mortality rate and values more than 2ml/kg increased mortality rate. Maximum increase in serum levels of liver enzymes was observed 24 hours after injection of CCl4 (at the dose of 1.5ml/kg), which decreased gradually. The degree of liver damage in days after the injection was the same until the fourth day, but the liver regeneration phasewas initiated after 72 hours.

According to the results of this study, a single intraperitoneal administration of CCl4 at the dose of 1.5mL/kg CCl4 could be an appropriate dosage for the production of a model of acute hepatic failure in NMRI mouse.