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Published on: May 13, 2016
Experimental model of hepatic fibrosis following repeated periportal necrosis induced by allylalcohol
S A Jung1, Y H Chung, N H Park
1Dept. of Internal Medicine, Asan Medical Center, Ewha Womans University College of Medicine, Seoul, Korea.
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.
Insights
Repetitive allylalcohol injections in rats effectively induced hepatic fibrosis, particularly in the periportal zone. This model shows increased collagen and transforming growth factor-beta1 (TGF-β1) mRNA, useful for studying liver fibrosis.
Area of Science:
- Hepatology
- Fibrosis Research
- Animal Models
Background:
- Chronic viral hepatitis often features periportal hepatic necrosis and fibrosis.
- A simple rat model for hepatic fibrosis was needed, mimicking periportal damage.
Purpose of the Study:
- To establish a novel, simple rat model of hepatic fibrosis.
- To induce repetitive periportal necrosis using allylalcohol.
Main Methods:
- Adult male rats received intraperitoneal allylalcohol injections twice weekly.
- Liver tissues were analyzed for fibrosis extent, collagen content, and transforming growth factor-beta1 (TGF-β1) mRNA expression via RT-PCR.
- Control rats received normal saline.
Main Results:
- Moderate to severe periportal fibrosis was observed in rats after 8 weeks of allylalcohol treatment.
- Significant correlations were found between fibrosis extent, collagen levels, and TGF-β1 mRNA expression.
- TGF-β1 mRNA levels were upregulated in liver tissues with significant fibrosis.
Conclusions:
- Repetitive allylalcohol injections (0.62 mmol/kg, twice weekly for 8 weeks) reliably induce hepatic fibrosis in rats.
- This model exhibits TGF-β1 overexpression and is suitable for studying predominantly periportal fibrosis.
- The model aids research into liver fibrosis mechanisms and potential therapies.
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