Hepatoprotective effects of diosmin and/or sildenafil against cholestatic liver cirrhosis: The role of Keap-1/Nrf-2 and P38 -MAPK/NF-κB/iNOS signaling pathway

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
Fares E M AliRamadan A M Hemeida

Abstract

The present study was designed to investigate the potential protective effects of diosmin (DS) and/or sildenafil against bile duct ligation (BDL). In order to achieve this goal, BDL was performed to induce liver cirrhosis, DS (100 mg/kg/day, p.o.) and sildenafil (10 mg/kg, twice daily, p.o.) were administrated alone or in combination 24 h after the surgical operation and lasted for 4 weeks. Liver function biomarkers, fibrotic markers, oxidative stress markers, mRNA expression of NF-κB-p65, P38-MAPK, Nrf-2, and Keap-1, as well as protein expression of cytoglobin, NF-κB-p65, Nrf-2, iNOS and eNOS were investigated concomitantly with histopathological study. The results revealed that, 4 weeks of BDL induced a significant alteration in liver functions, fibrotic and oxidative stress markers. Furthermore, up-regulation of NF-κB-p65, P38-MAPK, Keap-1 and iNOS concomitantly with down-regulation of Nrf-2, cytoglobin and eNOS expressions were observed after BDL. DS and/or sildenafil treatment significantly alleviated the disturbance induced by BDL. These findings were further supported by the improvement in histopathological features. Additionally, co-administration of DS and sildenafil were found to significantly improved liver defects d...Continue Reading

Citations

Jun 27, 2020·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Rasha A ElmansyFares E M Ali
Feb 13, 2020·Investigational New Drugs·Hendawy OmOsama M Morsy
Sep 3, 2020·International Journal of Molecular Sciences·Wolfgang KreiselPeter Deibert
Feb 7, 2020·Phytotherapy Research : PTR·Xiao MaYanling Zhao
Nov 1, 2020·Environmental Science and Pollution Research International·Emad H M HassaneinOmnia A M Abd El-Ghafar
Nov 24, 2020·Fundamental & Clinical Pharmacology·Moein AlaAhmad Reza Dehpour
Jan 12, 2021·Saudi Journal of Biological Sciences·Sayeed Mohammed FirdousMourad A M Aboul-Soud
Apr 2, 2021·Environmental Science and Pollution Research International·Emad H M HassaneinSouty M Z Sharkawi
Oct 12, 2021·Frontiers in Medicine·Thit Mynster KronborgNina Kimer
Oct 24, 2021·European Journal of Drug Metabolism and Pharmacokinetics·Samar H GergesEbtehal El-Demerdash
Dec 18, 2021·Drug and Chemical Toxicology·Nayeon YangTaekyun Shin

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