Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Sevoflurane alleviates liver ischemia reperfusion injury through inactivation of the TRAF6/NF-κB signaling pathway

Hongqiang Liu¹, Ying Yuan², Dan Rao¹

¹Department of General Surgery; ²Department of Anesthesia, The Ninth People's Hospital of Chongqing, Chongqing City 400700, China.

For correspondence:- Dan Rao Email: raodan0603@163.com Tel:+8623-68281801

Accepted: 29 September 2021 Published: 31 October 2021

Citation: Liu H, Yuan Y, Rao D. Sevoflurane alleviates liver ischemia reperfusion injury through inactivation of the TRAF6/NF-κB signaling pathway. Trop J Pharm Res 2021; 20(10):2043-2048 doi: 10.4314/tjpr.v20i10.5

© 2021 The authors.
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Abstract

Purpose: To evaluate the role and mechanism of action of sevoflurane in liver ischemia reperfusion injury.

Methods: Rats were pretreated with sevoflurane and then underwent liver ischemia followed by reperfusion to establish an animal model of liver ischemia reperfusion injury. Pathological changes in liver tissues were investigated by hematoxylin and eosin (H & E) staining, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using a chemistry analyzer. ELISA was used to determine the levels of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), IL-6, superoxide (SOD), malonaldehyde (MDA), catalase (CAT), and glutathione (GSH).

Results: Pathological changes in liver tissue, including sinusoidal congestion, vacuole formation, and infiltration of inflammatory cells and lymphocytes, were identified in rats post-ischemia reperfusion injury. In addition, serum ALT and AST levels increased following ischemia reperfusion injury. However, administration of sevoflurane ameliorated the pathological liver damage and decreased the serum ALT and AST levels induced by ischemia reperfusion. Pro-inflammatory cytokines, such as MPO, TNF-α, IL-1β, and IL-6 were upregulated in rats following ischemia reperfusion injury, and this upregulation was reversed by sevoflurane administration. Sevoflurane administration also attenuated the ischemia reperfusion-induced increase in MDA and decrease in SOD, CAT, and GSH. Ischemia reperfusion repressed IκBα protein expression and promoted protein expression of TNF receptor associated factor 6 (TRAF6), phospho (p)-IκBα, and p-p65 in liver tissue. However, sevoflurane reversed the effect of ischemia reperfusion on IκBα, TRAF6, p-IκBα, and p-65 expression.

Conclusion: Sevoflurane administration reduced pathological liver injury post-ischemia reperfusion by suppressing the inflammatory response and oxidative stress through inactivation of the TRAF6/NF-κB pathway.

Keywords: Sevoflurane, Liver ischemia reperfusion, Pathological injury, Inflammation, Oxidative stress, TRAF, NF-κB