Silybin prevented avermectin-induced cardiotoxicity in carp by modulating oxidative stress, inflammation, endoplasmic reticulum stress, mitochondrial apoptosis, and autophagy

Jiajie Gan; Haoming Ma; Yeyun Ma; Mengyuan Zhou; Ying Li; Weiping Yan; Zibo Dong

doi:10.1016/j.fsi.2024.109624

Silybin prevented avermectin-induced cardiotoxicity in carp by modulating oxidative stress, inflammation, endoplasmic reticulum stress, mitochondrial apoptosis, and autophagy

Fish Shellfish Immunol. 2024 May 11:150:109624. doi: 10.1016/j.fsi.2024.109624. Online ahead of print.

Authors

Jiajie Gan¹, Haoming Ma², Yeyun Ma¹, Mengyuan Zhou¹, Ying Li¹, Weiping Yan¹, Zibo Dong³

Affiliations

¹ Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
² Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China; School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, China.
³ Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address: 2018000011@jou.edu.cn.

PMID: 38740228
DOI: 10.1016/j.fsi.2024.109624

Abstract

Avermectin is one of the widely used anthelmintics in aquaculture and exhibits substantial toxicity to aquatic organisms. Silybin is extensively used for its anti-inflammatory, antioxidant and anti-apoptotic biological properties. Heart is essential for the survival of fish and plays a vital role in pumping blood oxygen and nutrients. Residual avermectin in water poses harm to carp. However, there is still insufficient research on whether silybin can mitigate the toxicity of avermectin to carp heart tissues. In this research, we established a model involving carp subjected to acute avermectin exposure and administered diets containing silybin to explore the potential protective effects of silybin against avermectin-induced cardiotoxicity. The results revealed that avermectin induced oxidative stress, inflammation, endoplasmic reticulum (ER) stress, mitochondrial pathway apoptosis and autophagy in the cardiac tissues of carp. Compared with the avermectin group, silybin significantly reduced ROS accumulation in cardiac tissues, restored antioxidant enzyme activity, inhibited mRNA transcript levels of pro-inflammatory-related factors, and attenuated ER stress, mitochondrial pathway apoptosis and autophagy. Protein-protein interaction (PPI) analysis demonstrated that silybin mitigated avermectin-induced cardiac oxidative stress, inflammation, ER stress, mitochondrial pathway apoptosis and autophagy. Silybin exerted anti-inflammatory effects through the Nuclear Factor kappa B (NF-κB) pathway, antioxidant effects through the Nuclear factor erythroid 2-related factor 2 (Nrf2) - Kelch-like ECH-associated protein 1 (Keap1) pathway, alleviated cardiac ER stress through the Glucose-regulated protein 78 (GRP78)/Activating Transcription Factor 6 (ATF6)/C/EBP homologous protein (CHOP) axis, suppressed apoptosis through the mitochondrial pathway, and inhibited excessive autophagy initiation through the PTEN-induced putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin protein ligase (PARKIN) signaling pathway. This study provided evidence supporting the protective effect of silybin against avermectin-induced cardiotoxicity in carp, highlighting its potential as a dietary additive to protect fish from adverse effects caused by avermectin exposure.

Keywords: Autophagy; Avermectin; Endoplasmic reticulum stress; Mitochondrial pathway apoptosis; Oxidative stress; Silybin.