PHARMACOLOGICAL EVALUATION OF BETA‐HYDROXIPHOSPHOCARNITINE IN NO‐ALCOHOLIC ESTEATOHEPATITIS INDUCED IN RATS

Abstract

ObjectiveTo evaluate the pharmacological effect of Β‐Hydroxyphosphocarnitine (β‐HFC) on non‐alcoholic steatohepatitis induced in rats.IntroductionNon‐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.MethodEHGNA 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.ResultsIn 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.ConclusionB‐HFC reduced liver damage levels in rats with EHGNA.