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Midazolam Ameliorates Acute Liver Injury Induced by Carbon Tetrachloride via Enhancing Nrf2 Signaling Pathway.
- Source :
- Frontiers in Pharmacology; 7/8/2022, Vol. 13, p1-12, 12p
- Publication Year :
- 2022
-
Abstract
- Oxidative stress contributes greatly to initiation and progression of liver injury. Activation of nuclear-factor erythroid 2-related factor 2 (Nrf2) has been considered as an attractive strategy for preventing and treating the oxidative damage related to liver injury. This study aimed to find an efficacious agent to activate Nrf2/HO-1 signaling pathway from clinically used therapeutic agents and to characterize the usefulness for preventing and treating CCl4-induced acute liver injury. For this purpose, a series of clinically used therapeutic agents were collected and their activation potentials on Nrf2 were assayed by using 293TNrf2-luc cell line. Among all tested therapeutic agents, midazolam was found with good Nrf2 activation effect and this agent could significantly ameliorate CCl4-induced damage to HepG2 cells. In vivo animal tests showed that pretreatment with midazolam reduced the liver pathological tissue damage and the serum levels of ALT and AST in CCl4-induced liver injury mice. Further investigations showed that midazolam could strongly up-regulate the expression of both Nrf2 and HO-1 in the mice liver, accompanied by increasing of the levels of antioxidant enzyme SOD and reducing the production of MDA, as well as reducing the pro-inflammatory cytokines (IL-6, TNF-α) secretion. Collectively, our results clearly demonstrate that midazolam can ameliorate CCl4-induced acute liver injury and oxidative stress via activating the Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16639812
- Volume :
- 13
- Database :
- Complementary Index
- Journal :
- Frontiers in Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 160640688
- Full Text :
- https://doi.org/10.3389/fphar.2022.940137