Rapamycin-filgrastim combination therapy ameliorates portal hypertension-induced splenomegaly: Role of β actin and S۱۰۰A۹ proteins modulation

Objective(s): Thioacetamide (TAA) was administered to induce an animal model of liver disease with secondary splenomegaly to assess the mechanisms underlying the effects of rapamycin and filgrastim when taken separately or in combination on the biochemical and histopathological aspects of the liver and spleen. Materials and Methods: Thirty adult male albino rats were divided into five groups (control, TAA-treated group, TAA+rapamycin, TAA+filgrastim, and TAA+rapamycin+filgrastim group). We measured relative liver and spleen weights, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin. Molecular docking modeling and histopathological examination of liver and spleen sections with hematoxylin and eosin and Masson trichrome staining with immunohistochemical detection of splenic CD۳ and CD۲۰ lymphocytes, S۱۰۰A۹ and β actin antibodies were detected. Morphometric and statistical analyses of the results were performed. Results: TAA administration altered the histological structure of the liver and spleen and impaired liver function. It increased the expression of splenic CD۳, CD۲۰ lymphocytes, and S۱۰۰A۹ while diminishing the expression of β actin. Each of rapamycin and filgrastim, when administered separately, improved liver and spleen indices and liver function, but rapamycin did not affect the albumin level. They lowered splenic B and T lymphocyte levels. Expression levels of S۱۰۰A۹ showed down-regulation while β actin levels were up-regulated when compared with TAA. Combination therapy improved liver and spleen tissue pathology and significantly ameliorated the expression of splenic lymphocytes through regulation of S۱۰۰A۹ and β actin expression. Conclusion: The synergistic effect of combination therapy was dependent on the regulation of splenic S۱۰۰A۹ and β actin levels.

کلیدواژه ها:

Actins ، Filgrastim ، Hypertension ، Portal ، Sirolimus ، splenomegaly