Characteristics of early–stage fibrosis model in chronic alcoholic liver disease in rats

BACKGROUND: The early stage of liver fibrosis of alcoholic or drug-induced origin in humans is difficult to diagnose because it is often asymptomatic. Developing experimental models of the early stages of liver fibrosis that closely reproduce clinical characteristics and allow for the evaluation of candidate hepatoprotective agents for the prevention and treatment of fibrosis is an important task in hepatology.

AIM: This work aimed to develop a model of the early stage of liver fibrosis with evaluation of typical pathomorphological and biochemical indicators of chronic alcoholic liver disease in rats.

METHODS: The study was conducted on 20 white outbred male rats weighing 270–315 g, which were divided into 2 groups: experimental and control (n = 10 per group). Alcohol-induced liver injury was modeled by intragastric administration of 40% ethanol at 5 g/kg for the first 14 days and 3.75 g/kg for the subsequent 14 days. Throughout the experiment, general condition, body weight, and mortality were monitored. At the end of ethanol administration, animals were euthanized; blood was collected for biochemical analysis, and liver tissue was collected to determine S-adenosylmethionine concentration and perform histological examination. The severity of fibrosis was assessed using the METAVIR score, and the liver mass coefficient was determined.

RESULTS: The induced alcoholic liver disease was characterized by mortality and neurological disturbances, including increased aggressiveness and slowed body weight gain compared with controls. Mortality in the experimental group (2 rats) occurred on day 13 after the start of ethanol administration. Biochemical analysis demonstrated increased aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase activity, as well as a decrease in the R-factor and reduced synthesis of S-adenosylmethionine in the liver. Liver dysfunction was accompanied by a reduction in the liver mass coefficient, nucleomegaly and steatosis, and moderate hepatofibrosis (stage F2 according to METAVIR), due to collagen fiber proliferation around bile ducts in portal tracts and the initiation of porto-portal septa formation.

CONCLUSION: The model successfully reproduced characteristic features of alcoholic liver disease and can be recommended for studying the pathogenesis and early stages of liver cirrhosis, as well as for the screening and evaluation of candidate hepatoprotective and antifibrotic agents.