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

β-羟基磷酸肉碱可改善大鼠非酒精性脂肪性肝炎的纤维化、脂肪变性并改善肝功能

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作者:Janet Sánchez-Quevedo, Emmanuel Ocampo-Rodríguez, Elizabeth Alvarez-Ayala, Anahí Rodríguez-López, Miguel Angel Duarte-Vázquez, Jorge Luis Rosado, Lourdes Rodríguez-Fragoso

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

Conclusions

Our research shows that β-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting β-HPC could be potentially used in the treatment of NASH.

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 β-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. α-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 α-SMA positive cells in fibrosis areas. The over-expression of SREBP-1 in cytoplasm and nuclei was evident. Animals with NASH treated with β-HPC showed a significant reduction in inflammation, necrosis, and glycogen content in the liver. A reduction in α-SMA and SREBP-1 immunopositive cells correlated with a significant reduction in the degree of fibrosis and steatosis found in liver tissue. β-HPC reduced the levels of ALP and GGT, and significantly reduced triglyceride levels. Animals treated with β-HPC did not show any alterations in liver enzyme function. Conclusions: Our research shows that β-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting β-HPC could be potentially used in the treatment of NASH.

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