Experimental model of hepatic fibrosis following repeated periportal necrosis induced by allylalcohol.

BACKGROUND/AIMS: In most patients with chronic viral hepatitis the predominant lobular location of hepatic necrosis and fibrosis is the periportal zone. We established a new simple model of hepatic fibrosis in rats by repetitive periportal necrosis with allylalcohol.

METHODS

Of 40 male adult rats, 30 were injected with 0.62 mmol/kg of allylalcohol intraperitoneally twice a week, the remaining 10 with normal saline as controls. Ten rats were killed at each of 4, 8, and 16 weeks later. The extent of fibrosis was evaluated according to the portal-portal extent. Transforming growth factor (TGF) beta1 mRNA in liver tissues was detected by reverse transcriptase polymerase chain reaction, and its levels were determined by the endpoint titers of serial two-fold dilutions of cDNA.

RESULTS

After 4 weeks, periportal fibrosis was produced in only 6 out of 10 rats, and was mild in extent. However, after 8 weeks, 8 out of 9 survivors showed moderate to severe fibrosis, which corresponded to a score of 7 or more. The extent of fibrosis correlated significantly with the amount of collagen and TGFbeta1 mRNA expression in liver tissues. The collagen content and expression of TGFbeta1 mRNA were also upregulated significantly in liver tissues with a fibrosis score of 7 or more.

CONCLUSIONS

Hepatic fibrosis can be sufficiently induced by repetitive intraperitoneal injection of 0.62 mmol/kg of allylalcohol twice a week for 8 weeks. This simple model of hepatic fibrosis, in which TGFbeta1 is overexpressed at the transcriptional level, may be useful in the study of patients who have predominantly periportal necrosis and fibrosis.