Beta-hydroxyphosphocarnitine modifies the inflammation in rats with non-alcoholic steatohepatitis

Abstract

<b>Abstract ID 17031</b> <b>Poster Board 52</b> <b>Objective:</b> To evaluate the pharmacological effect of β-Hydroxyphosphocarnitine (β-HPC) on inflammation in rats with non-alcoholic steatohepatitis. <b>Introduction:</b> Non-alcoholic steatohepatitis (NASH) is a disease characterized by the development of steatosis and an increase in inflammatory cytokines, leading to the development of fibrosis. Currently there is no specific drug for the treatment of NASH, given its high prevalence, the development of an effective drug for the wide spectrum of alterations that characterize NASH is urgently needed. <b>Method:</b> NASH was developed in male Wistar rats by the administration of a high fructose solution, saturated fat, and carbon tetrachloride. The rats were divided into six groups of treatment: (1) Control group, animals with no treatment; (2) β-HPC group (100 mg/Kg, orally for 4 weeks; (3) NASH group, animals received a fructose solution (10%, 400 kcal), a sutured fat solution (16 kcal) and carbon tetrachloride (CCl₄, 30%). The animals were allowed to ingest fructose solution ad libitum in place of drinking water, from the first day until the end of the study (9 weeks); and (4) NASH + β-HPC group, were treated as was described above. The animals were housed in con- trolled ambient temperature and humidity, maintained with a standard diet and had water ad libitum. The animals were treated in accordance with the Guide for the Care and Use for Laboratory Animals. The effect of β-HPC on inflammation was investigated by quantifying the inflammatory cytokines (IL-1β and TNF-α) levels by immunohistochemistry. A histopathological analysis of liver sections was also performed. The study was approved by an Institutional Review Board. <b>Results:</b> Presence of inflammation is key in the progress of NASH. It has been reported that IL-1β and TNF-α can influence in the development of steatosis and fibrosis. Therefore, it was interesting to evaluate the effect of β-HPC on these cytokines. Animals with NASH showed an increase in both, IL-1β and TNF-α expression (4.2 and 4.8-fold, respectively) as compared with control group (p&lt;0.05). However, in animals with NASH and treated with β-HPC, both IL-1β and TNF-α expression were significantly reduced (80% and 75%, respectively) as compared with NASH group (p&lt;0.05). The histopathological analysis revealed presence of micro and macrovesicular steatosis in NASH group. However, animals with NASH and treated with β-HPC showed a significant reduction in liver steatosis and as well as an improvement in liver architecture. The decrease in steatosis could explained by the reduction of IL-1β and TNF-α in these animals. Steatosis plays an important role for the activation of Kupffer cells and for the arriving inflammatory cells to liver. These results demonstrated the effect of β-HPC on inflammation in the development of NASH. <b>Conclusions:</b> Our results showed that β-HPC can modify steatosis and inflammation in rats with NASH. Further studies are necessary to elucidate the mechanism of action of β-HPC in non-alcoholic steatohepatitis.