Fares E M Ali1, Adel G Bakr2, Amira M Abo-Youssef3, Amany A Azouz3, Ramadan A M Hemeida2. 1. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt. Electronic address: FaresAli@azhar.edu.eg. 2. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt. 3. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Abstract
AIM: The 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 METHODS: Fifty 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 FINDINGS: Chronic 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 ameliorated the disturbance that occurred due to BDL. Similar findings were observed in liver histopathology. SIGNIFICANCE: DS and PTX could mitigate liver cirrhosis through modulation of Keap-1/Nrf-2/GSH and NF-κB-p65/p38-MAPK signaling pathways. In addition, we demonstrated that the hepatoprotective effect of DS and PTX is mediated by up-regulation of cytoglobin with inhibition of fibrotic reaction.
AIM: The 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 METHODS: Fifty 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 FINDINGS: Chronic 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 ameliorated the disturbance that occurred due to BDL. Similar findings were observed in liver histopathology. SIGNIFICANCE: DS and PTX could mitigate liver cirrhosis through modulation of Keap-1/Nrf-2/GSH and NF-κB-p65/p38-MAPK signaling pathways. In addition, we demonstrated that the hepatoprotective effect of DS and PTX is mediated by up-regulation of cytoglobin with inhibition of fibrotic reaction.
Authors: Esam O Kamel; Wail M Gad-Elrab; Mohammed A Ahmed; Zuhair M Mohammedsaleh; Emad H M Hassanein; Fares E M Ali Journal: Biol Trace Elem Res Date: 2022-05-19 Impact factor: 3.738
Authors: Angélica Saraí Jiménez-Osorio; Sinaí Jaen-Vega; Eduardo Fernández-Martínez; María Araceli Ortíz-Rodríguez; María Fernanda Martínez-Salazar; Reyna Cristina Jiménez-Sánchez; Olga Rocío Flores-Chávez; Esther Ramírez-Moreno; José Arias-Rico; Felipe Arteaga-García; Diego Estrada-Luna Journal: Int J Mol Sci Date: 2022-05-17 Impact factor: 6.208