β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats

Background: Non-alcoholic steatohepatitis (NASH) is a chronic disease characterized by inflammation, steatosis, and liver fibrosis. The liver is particularly affected by alterations in lipid metabolism. Our aim was to evaluate the effect of beta-hydroxyphosphocarnitine (beta-HPC) on NASH induced in rats. Methods: NASH was produced via the ad libitum daily chronic administration of a fructose solution (400 kcal) for 9 weeks, an oral dose of fat solution (16 kcal) for 7 weeks and a subcutaneous injection of CCl4 (30%) two times a week for 2 weeks to Wistar rats. To evaluate the effect of beta-HPC, a dose of 100 mg/kg was administered perorally for 4 weeks and its biochemical and hepatic effects on rats with NASH were analyzed. Serum levels of glucose, triglycerides, cholesterol, and liver enzymes were quantified. Histological changes were evaluated on slices stained with H&E, trichromic and PAS. Glycogen content was measured in liver samples. alpha-SMA and SREBP-1 immunopositive cells were identified in liver tissue. Results: NASH was characterized by elevated triglycerides, elevated liver damage enzymes, and the presence of necrosis, inflammation, steatosis, and fibrosis. Significant amounts of glycogen were found, along with alpha-SMA positive cells in fibrosis areas. The over-expression of SREBP-1 in cytoplasm and nuclei was evident. Animals with NASH treated with beta-HPC showed a significant reduction in inflammation, necrosis, and glycogen content in the liver. A reduction in alpha-SMA and SREBP-1 immunopositive cells correlated with a significant reduction in the degree of fibrosis and steatosis found in liver tissue. beta-HPC reduced the levels of ALP and GGT, and significantly reduced triglyceride levels. Animals treated with beta-HPC did not show any alterations in liver enzyme function. Conclusions: Our research shows that beta-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting beta-HPC could be potentially used in the treatment of NASH.