Pharmacological Evaluation of Beta‐Hydroxifosphocarnitine in No‐Alcoholic Steatohepatitis Induced in Rats

Abstract

Aim Evaluate the pharmacological effect of Β-Hydroxyphosphocarnitine (β-HFC) on non-alcoholic steatohepatitis induced in rats. Introduction Non-alcoholic steatohepatitis (NASH) is a disease with high prevalence, usually accompanied on metabolic syndrome. Currently the treatment to NASH 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 syndrome and maintaining its pharmacological properties. 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 NASH rats was evaluated by histological sections of the liver with Masson's hematoxylin eosin and trichromic staining. Quantification of liver enzymes, triglycerides, cholesterol and glucose in serum by spectrophotometric kit. Insulin levels were determined by Elisa. Results We previously reported that β-HFC reduced serum triglyceride levels in NASH rats. The levels of glucose, insulin and nitric oxide (NO) were quantified and are the ones that we will report on this occasion. Insulin levels were low in the NASH rats even with the β-HFC treatment compared to the control rats, (25.9 ± 6, 30.0 ± 10 and 121.1 ± 69.5 ng / ml respectively). The pancreas can be damaged by excess fatty acids (FA), altering insulin production. No significant difference was observed in glucose levels between the control and NASH groups (123.2 ± 50.6 and 134.3 ± 19.1 mg/dL respectively). High glucose levels would be expected in NASH rats, however, since insulin resistance is not observed, it could justify that glucose is not elevated. NO is a source of production of reactive species. The rats with NASH showed higher levels of NO than those of the control group (0.054, 0.01 µM / µl respectively). β-HFC was shown to reduce NO levels in rats with NASH (0.03µM / µl). β-HFC enhances the fatty acid oxidation process which can result in decreased production of reactive species. Conclusion: β-HFC enhances key alterations for NASH progression such as DNL and NO production. Conclusion: β-HFC promises to be effective for the treatment of NAHS by improving key alterations for the progression of NASH such as DNL and NO production.