Protective mechanisms of telmisartan against hepatic ischemia/reperfusion injury in rats may involve PPARγ-induced TLR4/NF-κB suppression
Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved..
Hepatic ischemia-reperfusion (I/R) is an important cause of liver damage in many clinical situations. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) is an inflammatory pathway activated in hepatic I/R injury. Telmisartan, a selective angiotensin II type 1 receptor antagonist and peroxisome proliferator-activated receptor-gamma (PPARγ) partial agonist, can inhibit the expression of pro-inflammatory cytokines. The present work investigated the possible protective effect of telmisartan against hepatic I/R injury and explored its possible mechanisms in rats. Rats were divided into four equal groups: sham-operated control, telmisartan-treated sham-operated control, I/R untreated, and I/R telmisartan-treated groups. Hepatic injury was evaluated biochemically by serum activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and histopathological examination. Hepatic oxidative stress biomarkers, myeloperoxidase level, PPARγ and TLR4 mRNA expression, and NF-κB and active caspase 3 immunoexpression were determined. The study showed that telmisartan attenuated hepatic I/R, as evidenced by decreased serum ALT and AST activities and confirmed by improvement of the histopathological changes. The protective effect of telmisartan was associated with modulation of oxidative stress parameters, myeloperoxidase level, PPARγ and TLR4 mRNA expression, and NF-κB and caspase 3 immunoexpression. Taken together, the current study showed that telmisartan could protect the rat liver from I/R injury. This hepatoprotective effect was attributed to, at least in part, increase in PPARγ expression and suppression of TLR4/NF-κB pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:145 |
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| Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 145(2022) vom: 09. Jan., Seite 112374 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Morsy, Mohamed A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.03.2022 Date Revised 03.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biopha.2021.112374 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM334518792 |
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| 520 | |a Hepatic ischemia-reperfusion (I/R) is an important cause of liver damage in many clinical situations. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) is an inflammatory pathway activated in hepatic I/R injury. Telmisartan, a selective angiotensin II type 1 receptor antagonist and peroxisome proliferator-activated receptor-gamma (PPARγ) partial agonist, can inhibit the expression of pro-inflammatory cytokines. The present work investigated the possible protective effect of telmisartan against hepatic I/R injury and explored its possible mechanisms in rats. Rats were divided into four equal groups: sham-operated control, telmisartan-treated sham-operated control, I/R untreated, and I/R telmisartan-treated groups. Hepatic injury was evaluated biochemically by serum activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and histopathological examination. Hepatic oxidative stress biomarkers, myeloperoxidase level, PPARγ and TLR4 mRNA expression, and NF-κB and active caspase 3 immunoexpression were determined. The study showed that telmisartan attenuated hepatic I/R, as evidenced by decreased serum ALT and AST activities and confirmed by improvement of the histopathological changes. The protective effect of telmisartan was associated with modulation of oxidative stress parameters, myeloperoxidase level, PPARγ and TLR4 mRNA expression, and NF-κB and caspase 3 immunoexpression. Taken together, the current study showed that telmisartan could protect the rat liver from I/R injury. This hepatoprotective effect was attributed to, at least in part, increase in PPARγ expression and suppression of TLR4/NF-κB pathway | ||
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