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

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.