Allantoin ameliorated liver fibrosis in a mouse model of non-alcoholic steatohepatitis: role of nuclear factor kappa B/cyclooxygenase 2/prostaglandin E2 pathway

Abstract

Introduction: Non-alcoholic steatohepatitis (NASH) is considered as current and critical liver disease and liver fibrosis is an initial step to vast NASH injuries. Allantoin is an important and sure composite, which has remark effects on inflammation and apoptosis. This study was done to evaluate the allantoin duty on liver fibrosis and its pathways in mice-induced NASH. Methods: In the control groups, inbred mice took saline and allantoin. In the NASH group, NASH was provided with a methionine-choline deficient (MCD) diet for eight weeks, and finally, in the NASH-Alla group, allantoin was injected for four weeks in the mice with an MCD diet. For collagen deposition evaluation, trichrome Masson staining and for cellular evaluations, real-time PCR and ELISA assays were performed. Results: Allantoin treatment improved liver steatosis and fibrosis. Protein expression of nuclear factor kappa B (NFĸB-p65) (P < 0.05) and genes expressions of transforming growth factor-β (TGFβ) (P < 0.001), cyclooxygenase 2 (COX2) (P < 0.001), matrix metalloproteinases 9 (MMP9) (P < 0.001) and alpha-smooth muscle actin (αSMA) (P < 0.001) were also decreased. Moreover, hepatic prostaglandin E2 (PGE2) levels lowered after allantoin treatment (P < 0.05).Conclusion: Attenuating effects of allantoin on liver fibrosis may be due to the inhibition of NFĸB/TGFβ, NFĸB/MMP9, and NFĸB/Cox2/PGE2 pathways, which decrease αSMA expression and collagen deposition and ameliorate liver fibrosis.

Keywords: Fibrosis, Non-alcoholic fatty liver disease, Matrix metalloproteinases 9, Alpha-smooth muscle actin, Transforming growth factor-β