Epicatechin attenuates emamectin benzoate-induced liver injury in grass carp by activating Nrf2/GPX4 signaling pathway

Xinhui Zhang; Fengyan Zhang; Musen Li; Qingsong Sun; Yuehong Li; Yunhe Fu; Yue Zhang

doi:10.1016/j.fsi.2025.110118

Epicatechin attenuates emamectin benzoate-induced liver injury in grass carp by activating Nrf2/GPX4 signaling pathway

Fish Shellfish Immunol. 2025 Jan 12:110118. doi: 10.1016/j.fsi.2025.110118. Online ahead of print.

Authors

Xinhui Zhang¹, Fengyan Zhang¹, Musen Li¹, Qingsong Sun¹, Yuehong Li², Yunhe Fu³, Yue Zhang⁴

Affiliations

¹ College of Animal Science and Technology, Jilin Agriculture Science and Technology University, Jilin City, China.
² College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.
³ Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, China.
⁴ College of Animal Science and Technology, Jilin Agriculture Science and Technology University, Jilin City, China. Electronic address: zhangyue127zy@163.com.

PMID: 39809417
DOI: 10.1016/j.fsi.2025.110118

Abstract

Emamectin benzoate (EMB) is an antibiotic insecticide pesticide modified from avermectin. In the current study, we performed an in-depth investigation of the protective effects of epicatechin on EMB-induced liver injury in common carps. The carps were cultured in an aquatic environment containing 2.4 μg/L of EMB for 30 days to establish the model. The results provide direct evidence that epicatechin could attenuate EMB-induced liver injury, as confirmed by the inhibition of epicatechin on EMB-induced liver pathological injury, serum glucose (GLU), cortisol (COR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), adenosine deaminase (ADA), and alkaline phosphatase (ALP) levels. Epicatechin also inhibited EMB-induced inflammation, as confirmed by the inhibition of epicatechin on tumor necrosis factor (TNF-α) and Interleukin-1β (IL-1β) production, and nuclear factor kappa-B (NF-κB) activation induced by EMB. Moreover, epicatechin could attenuate EMB-induced ferroptosis, as confirmed by the inhibition of epicatechin on malondialdehyde (MDA) and Fe²⁺ production, and up-regulation of Adenosine Triphosphate (ATP), Glutathione (GSH) production, and Glutathione Peroxidase 4 (Gpx4) and xCT expression. In addition, epicatechin increased the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). We therefore conclude that epicatechin protected EMB-induced liver injury by preventing ferroptosis through activating Nrf2.

Keywords: Emamectin benzoate; Nrf2; epicatechin; ferroptosis; liver injury.