Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Verteporfin mitigates sepsis-induced liver injury by blocking macrophage-derived inflammation

Yaopeng Yang¹, Anxiu Wang², Su Zhang¹, Guangming Peng¹, Haiying Wu³

¹Department of Emergency Medicine; ²Geriatric Department, People's Hospital of Yuxi City, Yuxi; ³Department of Emergency Medicine; The First Affiliated Hospital of Kunming Medical University, Kunming, China.

For correspondence:- Haiying Wu Email: why0209@hotmail.com Tel:+8613888533412

Accepted: 27 February 2022 Published: 31 March 2022

Citation: Yang Y, Wang A, Zhang S, Peng G, Wu H. Verteporfin mitigates sepsis-induced liver injury by blocking macrophage-derived inflammation. Trop J Pharm Res 2022; 21(3):529-535 doi: 10.4314/tjpr.v21i3.11

© 2022 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To study the role of yes-associated protein (YAP) inhibition by verteporfin (VTF) in LPS-induced acute liver injury (ALI) after sepsis.

Methods: In vitro, VTF was used to treat LPS-stimulated RAW 267.4 cells. In vivo, LPS was injected to induce sepsis in mice, followed by treatment with VTF. The inflammatory mediators were determined using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence spectroscopy (IF) and immunohistochemical staining (IHC), and the levels of YAP, P53 and ERK were measured by qRT-PCR, WB and IHC. Moreover, liver histology and liver function were examined using HE staining and ELISA respectively.

Results: The results showed that VTF reduced YAP expression and inhibited LPS-induced cell activation and inflammatory cytokine production such as IL-6 and IL-1β, by attenuating the expressions of p53 and ERK pathway in macrophages. The levels of AST, AIL and TBiL remarkably decreased in ALI mice after VTF treatment (p < 0.05). Moreover, it was observed that inflammatory mediators, including inducible nitric oxide synthase (iNOS), IL-6 and IL-1β, decreased significantly in VTF treated mice (P < 0.05).

Conclusion: VTF plays an antagonistic role in LPS-induced inflammatory response after ALI. Therefore, VTF is a potential medicinal agent for preventing infectious acute liver injury.

Keywords: Verteporfin, Sepsis, Liver injury, Macrophage, Inflammation