Liver structure and fibrosis markers in modeling alcohol-induced liver injury and correction of detected disorders

Abstract

Background. Chronic alcohol use leads to alcoholic liver fibrosis. Today, a sufficient number of scientific studies are focused on the pathometabolic mechanisms of liver fibrosis development and formation in animal models. The purpose of our study was to investigate structural changes and liver stiffness, biochemical markers of fibrosis in rats with chronic alcoholic liver injury (CALI) modeling and to evaluate the changes of these parame­ters with different types of treatment. Materials and methods. Eighty-nine rats were divided into experimental groups depending on the duration of alcohol exposure (4 and 12 weeks) and the corresponding type of correction (metadoxine and prebiotic). Results. When modeling CALI at week 4, morphological studies revealed moderate large-droplet fatty hepatosis and mild fibrosis in the central venule of the liver lobes. After 12 weeks of forced alcoholization, with more pronounced general intoxication, hepatocytes have dystrophic changes such as appearance of single or grouped dystrophic cells in the parenchyma. A combination of protein and fatty dystrophy was more common. Elastography allowed to detect structural changes in the liver at the early stages of fibrosis formation when modeling CALI for 12 weeks. There were also changes in the levels of biochemical parameters: free and protein-bound hydroxyproline, glycosaminoglycans. According to the results of elastography, liver stiffness in rats increased maximally after prebiotic correction in all approaches compared to the controls. After correction of CALI, both early- and long-term, fibrosis markers normalized in rat liver homogenate after administration of metadoxine and prebiotic. After prebiotic correction at week 12 of alcoholization, we observed a 12% decrease in liver parenchymal stiffness in the CALI modeling group and a 19% decrease (p < 0.05) in the placebo group. After correction with metadoxine, there was a 1.5-fold increase in free hydroxyproline levels in rat liver homogenate at week 12 and a 1.2-fold increase in glycosaminoglycans (p < 0.05) at week 4 compared to the CALI modeling group. Conclusions. Long-term alcoholization of animals led to the development of dystrophic changes in hepatocytes, protein and fatty degeneration, and an increase in the number of capillaries. Against this background, liver stiffness and biochemical parameters changed. After correction with metadoxine and prebiotic, changes in the liver stiffness and fibrosis markers were observed at week 12 of CALI modeling.

Keywords

• fibrosis
• chronic liver damage
• hydroxyproline
• glycosaminoglycans
• liver stiffness
• morphological studies