Targeting Keap-1/Nrf-2 pathway and cytoglobin as a potential protective mechanism of diosmin and pentoxifylline against cholestatic liver cirrhosis

Publication date: 15 August 2018Source: Life Sciences, Volume 207Author(s): Fares E.M. Ali, Adel G. Bakr, Amira M. Abo-youssef, Amany A. Azouz, Ramadan A.M. HemeidaAbstractAimThe effects of diosmin (DS), pentoxifylline (PTX) and their combination on inflammatory response, oxidant/antioxidant balance, cytoglobin and cirrhotic reaction during bile duct ligation (BDL) were investigated and explored.Main methodsFifty adult male Wistar albino rats were randomly allocated to five groups as following, sham: received vehicle only, BDL: subjected to common BDL without treatment, BDL plus DS: received 100 mg/kg/day orally, BDL plus PTX: received 50 mg/kg/day orally, BDL plus DS plus PTX: received DS and PTX in the same manner. The test period lasted 28 days, liver tissues and blood samples were collected to investigate biochemical markers (liver function biomarkers, oxidative stress markers, and antifibrotic markers), mRNA expression of Nrf-2, Keap-1, NF-κB-p65 and p38-MAPK by real-time PCR, protein expression of cytoglobin and NF-κB-p65 by western blot and iNOS and eNOS by immunohistochemistry. Histopathological study was performed to confirm our results.Key findingsChronic BDL induced a significant alteration in liver functions, oxidative stress and fibrotic markers. Furthermore, unfavorable effects on gene and protein expression were observed after BDL. Histopathological findings of this group showed parallel effects. DS, PTX and their combination treatment significantly ame...
Source: Life Sciences - Category: Biology Source Type: research