Inhibition of fucosylation by 2-fluorofucose attenuated acetaminophen-induced liver injury via its anti-inflammation and anti-oxidative stress effects

Zhaoguo Liu; Mengjue Tu; Jianan Shi; Hong Zhou; Guoliang Meng; Jianguo Gu; Yuqin Wang

doi:10.3389/fphar.2022.939317

Inhibition of fucosylation by 2-fluorofucose attenuated acetaminophen-induced liver injury via its anti-inflammation and anti-oxidative stress effects

Front Pharmacol. 2022 Sep 1:13:939317. doi: 10.3389/fphar.2022.939317. eCollection 2022.

Authors

Zhaoguo Liu¹, Mengjue Tu¹, Jianan Shi¹, Hong Zhou¹, Guoliang Meng¹, Jianguo Gu², Yuqin Wang¹

Affiliations

¹ Department of Pharmacology, School of Pharmacy and Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, Nantong University, Nantong, China.
² Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan.

Abstract

Fucosylation is a common glycan terminal modification, which has been reported to be inhibited by 2-fluorofucose (2FF) both in vivo and in vitro. The present study aimed to investigate the effect of 2FF on acetaminophen (APAP)-induced acute liver injury, and further clarified the possible mechanisms. In the present study, inhibition of fucosylation by 2FF relieved APAP-induced acute liver injury in vivo. Pretreatment with 2FF remarkably suppressed APAP-induced oxidative stress and mitochondria damage. 2FF markedly enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and simultaneously promoted the expression of downstream proteins including HO-1 and NQO1. Furthermore, pretreatment with 2FF significantly suppressed the expression of inflammation-associated proteins, such as COX2 and iNOS. The data from lectin blot assay revealed that the alteration of α1,6-fucosylation was involved in APAP-induced acute liver injury. The second part of this study further confirmed that the enhancements to antioxidant capacity of 2FF pretreatment and α1,6-fucose deficiency were related to Nrf2/keap1 and NF-κB signaling pathways in HepG2 cells. Taken together, the current study suggested that 2FF might have a potential therapeutic effect for APAP-induced acute liver injury.

Keywords: 2-fluorofucose; acetaminophen; fucosylation; liver injury; oxidative stress.