ABSTRACT
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.
Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Carnitine/analogs & derivatives , Cholesterol , Diet, High-Fat , Disease Models, Animal , Fructose/metabolism , Fructose/pharmacology , Fructose/therapeutic use , Glucose/metabolism , Glycogen/metabolism , Glycogen/pharmacology , Glycogen/therapeutic use , Inflammation/drug therapy , Liver , Liver Cirrhosis/metabolism , Necrosis , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Organophosphates , Rats , Rats, Wistar , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/pharmacology , TriglyceridesABSTRACT
Beta-casein (BC) in cow's milk occurs in several genetic variants, where BC A1 (BCA1) and BC A2 (BCA2) are the most frequent. This work deals with a method based on modified polyacrylamide gel electrophoresis using urea PAGE to discriminate BCA1 and BCA2 variants from Holstein Friesian (HF) and genetically selected Jersey A2/A2 (JA2) cow's milk. Two well defined bands were obtained from BC fraction of HF milk, while that of JA2 showed a single band. Proteins from these bands were sequenced by HPLC-quadrupole linear ion trap/mass spectrometry, resulting in BCA1 and BCA2 separation from the BC fraction of HF milk, whereas BCA2 was the only constituent of JA2 fraction. This method represents a feasible and useful tool to on site phenotyping of BC fraction of cow's milk for pharmaceutical and food industries applications.
ABSTRACT
The purpose of this research was to describe the pharmacokinetic parameters of ß-hydroxyphosphocarnitine (ß-HPC; CAS No. 1220955-20-3) after a single oral dose in rats and rabbits as well as to assess the impact of 14 weeks of ß-HPC (100 mg/kg) treatment on the serum metabolites and liver enzymes, body weight, and hepatic steatosis of lean and obese Zucker fa/fa rats. In the case of the rat and rabbit study, the ß-HPC area under the curve, biological half-life, and clearance were 2,174.4 versus 3,128 µg â h/ml, 23.7 versus 8.87 h, and 13.9 versus 151.1 ml/h in the rats versus the rabbits, respectively. The values for the time of maximal concentration were 0.58 versus 1.53 h, for the maximal concentration, they were 62.4 versus 221.4 µg/ml, and for the absorption rate constant 0.02 versus 2.40 h(-1), respectively. In the case of the Zucker fa/fa rat study, ß-HPC administered orally once a day reduced insulin, triglyceride, and cholesterol levels in the liver and serum; it also reduced weight gain and decreased liver steatosis in obese rats after 14 weeks. ß-HPC could therefore potentially be used in the treatment of metabolic syndrome.
