RESUMO

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 ß-hydroxyphosphocarnitine (ß-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 ß-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 ß-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. ß-HPC reduced the levels of ALP and GGT, and significantly reduced triglyceride levels. Animals treated with ß-HPC did not show any alterations in liver enzyme function. CONCLUSIONS: Our research shows that ß-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting ß-HPC could be potentially used in the treatment of NASH.

Assuntos

Hepatopatia Gordurosa não Alcoólica , Animais , Carnitina/análogos & derivados , Colesterol , Dieta Hiperlipídica , Modelos Animais de Doenças , Frutose/metabolismo , Frutose/farmacologia , Frutose/uso terapêutico , Glucose/metabolismo , Glicogênio/metabolismo , Glicogênio/farmacologia , Glicogênio/uso terapêutico , Inflamação/tratamento farmacológico , Fígado , Cirrose Hepática/metabolismo , Necrose , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Organofosfatos , Ratos , Ratos Wistar , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/farmacologia , Triglicerídeos

RESUMO

This review examined a collection of studies regarding the molecular properties of some polyene antibiotic molecules as well as their properties in solution and in particular environmental conditions. We also looked into the proposed mechanism of action of polyenes, where membrane properties play a crucial role. Given the interest in polyene antibiotics as therapeutic agents, we looked into alternative ways of reducing their collateral toxicity, including semi-synthesis of derivatives and new formulations. We follow with studies on the role of membrane structure and, finally, recent developments regarding the most important clinical applications of these compounds.