Pharmacological evaluation of the immunomodulatory FL-6 in induced chronic hepatitis in Wistar rats.

Abstract

The aim of this study was to evaluate the pharmacological effect of FL-6, a new immunomodulatory drug, in chronic hepatitis immunologically induced in rats via porcine-serum (PS) administration. Thirty-two male Wistar rats (150 g) were divided into 4 experimental groups: (1) Control (PBS 0.5 ml 3-times per week for 8-week); (2) FL-6 (50 ng/kg 3-times per week for 4-week); (3) Hepatitis (PS 373 mg/kg twice per week for 8-week); and (4) Hepatitis + FL-6 (doses as above). Rats were sacrificed at the end of treatment. ALT, AST, ALP and gamma-GT activities, as well as IL-6 and IL-10 levels, were evaluated in serum samples. Glutathione and malondialdehyde were also analyzed. A morphological analysis of liver tissue was carried out. The hepatitis group showed an increase in ALT (1.44-fold), AST (1.28-fold), ALP (1.83-fold), gamma-GT (3.91-fold), IL-6 (2.6-fold) and IL-10 (7.1-fold) levels when compared with controls (p < 0.05). Histopathological analysis revealed an inflammatory response characterized by inflammatory infiltrates and liver damage, which was accompanied by a reduction of 74.8% in glutathione levels (p < 0.05). However, animals with hepatitis treated with FL-6 had a reduction of ALT activity (17.74%), as well as a reduction in IL-6 (24.21%) and IL-10 (30.91%) levels (p < 0.05). These animals showed a reduction in inflammatory response characterized by a decrease in inflammatory infiltrate at the hepatic parenchyma and portal structures; livers showed less damage and a reduction of necrotic and apoptotic hepatocytes. In conclusion, the treatment with FL-6 improved liver function and reduced the inflammatory marker in rats with chronic hepatitis induced by PS-administration.