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 β-hydroxyphosphocarnitine (β-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 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.

Objective To evaluate the pharmacological effect of Β‐Hydroxyphosphocarnitine (β‐HFC) on non‐alcoholic steatohepatitis induced in rats. Introduction Non‐alcoholic fatty liver disease (EHGNA) is a disease with high prevalence, usually accompanied by metabolic syndrome. Currently the treatment to EHGNA is pioglitazone. However, it is reported that pioglitazone causes several side effects reason to stop treatment. L‐carnitine has pharmacological effect in the metabolic syndrome, but it is poorly absorbed. The β‐HFC is an analogue of L‐carnitine that has shown effect on metabolic síndrome and maintaining its pharmacological properties. Method EHGNA was developed in male Wistar rats with a mixed diet based on coconut oil, carbon tetrachloride and high fructose drink. The treatments were as follows: Without treatment, pioglitazone and β‐HFC in healthy groups and with EHGNA. Histological sections of the liver were made and stained with Masson's Trichromic Stain to see collagen fibers and Hematoxylin & Eosin to see hepatocyte morphology. Quantities of liver enzymes Aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) and triglycerides were performed. Results In the histology of the healthy control rats, the hepatocyte architecture is well observed, no liver damage characteristics are observed, for example: fat drops, inflammatory cells, necrosis, apoptosis and hepatocytes in the balloon. Healthy groups administered with pioglitazone and β‐HFC as well as the control show no characteristics of liver damage. Histologies of rats with EHGNA showed the characteristics of liver damage and greater amount of collagen fibers. Rats with steatophepatitis treated with β‐HFC showed reduced hepatocyte damage and fibrosis compared to EHGNA control rats. Liver enzyme levels increased 2.5 times more in the steatohepatitis group compared to those in control rats. Liver enzyme levels showed considerable reduction in those rats with statohepatitis and were treated with β‐HFC, showing values for the enzymes ALT, AST, GGT and ALP 85.79, 101.3, 3.2 and 556.4 U/L, respectively for group with steatohepatitis and 74.34, 77.7, 1.0 and 327 U/L, respectively for the group with steatohepatitis treated with β‐HFC. Triglyceride levels increased in rats with steatohepatitis compared to those in control rats and reduction in levels was observed for those who were treated with β‐HFC showing values of 63.7 (control), 255.1 (steatohepatitis) and 48.4 mg/dL (steatohepatitis + β‐HFC). The same behavior showed liver levels 0.04, 0.14 and 0.04 mg/dL respectively. Conclusion B‐HFC reduced liver damage levels in rats with EHGNA.

ID 17031 Poster Board 52Objective: To evaluate the pharmacological effect of b-Hydroxyphosphocarnitine (b-HPC) on inflammation in rats with non-alcoholic steatohepatitis.

Chronic liver disease affects globally and has a high morbidity and mortality rate. It is histopathologically characterized by the presence of inflammation, and the progressive destruction and regeneration of the hepatic parenchyma, which can lead to the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Most liver diseases tend to become chronic and can be therefore studied in animal models, as it is possible to quickly develop pathological processes in animals with a high degree of reproducibility and obtain predictive data regarding the different hepatopathies. The development of animal models in the field of hepatology has been geared toward the search for new knowledge meant to favor human well-being and proved useful in translational medicine focused on liver disease. Like any other methodological tool, animal models provide valuable. Obviously, a single model cannot reproduce the complexity and spectrum of all liver diseases, which is why a wide variety are currently employed: they include chemically, immune, diet, surgically, and genetically modified damage in animals and involve biological agents or the use of humanized livers in rodents. This chapter surveys some of the main animal models used in the study of chronic liver disease and the disease characteristics they mimic.

Aim Evaluate the pharmacological effect of Β‐Hydroxyphosphocarnitine (β‐HFC) on non‐alcoholic steatohepatitis induced in rats. Introduction Nonalcoholic steatotepatitis (NASH) is a serious global public health problem, it is related to other pathologies with increasing prevalence, manifested in the increased prevalence of NASH. Type 2 diabetes mellitus and obesity are the main pathologies related to NASH. There is no specific drug for NASH, the current drugs used for NASH are related to serious side effects, which is why there is an urgent need in the development of an effective therapy for NASH but with fewer side effects. L‐carnitine has an effect on improving metabolic alterations related to NASH, however, its intestinal absorption is limited. B‐HFC is an analog of L‐carnitine that has been shown to be safe for administration, to maintain pharmacological properties of its precursor and its absorption is greater than that of L‐carnitine. So it can be a good treatment for NASH. Method The NASH model was developed in male Wistar rats by ingesting carbonated drink as a source of fructose, coconut oil and carbon tetrachloride. 3 groups were formed with NASH (n = 8); NASH, NASH ‐β‐HFC and NASH‐pioglitazone. Another 3 groups of healthy rats (n = 8); control, control‐β‐HFC and control‐pioglitazone. The effect of β‐HFC in rats with NASH was evaluated by staining of histological sections of liver. The stains used were Masson's trichrome, hematoxylin and osin and Periodic Acid‐Schiff (PAS). Biochemical analysis was performed to evaluate the effect of β‐HFC on the metabolic alterations that characterize NASH. Result It was previously reported that β‐HFC reduced the triglyceride levels of rats with NASH, as well as the levels of liver enzymes. Evidencing the effect of β‐HFC in improving lipid metabolism, manifesting itself in less liver damage. For this occasion we will report the effect of β‐HFC on liver glycogen levels. Glycogen is a reserve of the cell, as a source of glucose in prolonged fasting states. Our results demonstrated a higher glycogen reserve in the NASH rats. This result was expected, since the rats had a high fructose intake. It is important to mention that the rats with NASH but treated with β‐HFC presented reduced glycogen levels, this effect can be attributed to a more efficient β‐oxidation process, which could also justify the reduction of triglycerides and fibrosis. Therefore, we could argue that a longer treatment time, the liver alterations in NASH would improve significantly. Conclusion β‐HFC has an effect on improving liver and metabolic alterations characteristic of the development of NASH.