Ferulic acid alleviates avermectin induced renal injury in carp by inhibiting inflammation, oxidative stress and apoptosis

Qiulu Li; Kaixin Ping; Yannan Xiang; Ying Sun; Zunhan Hu; Shujuan Liu; Xinying Guan; Mian Fu

doi:10.1016/j.fsi.2024.109575

Ferulic acid alleviates avermectin induced renal injury in carp by inhibiting inflammation, oxidative stress and apoptosis

Fish Shellfish Immunol. 2024 Apr 24:149:109575. doi: 10.1016/j.fsi.2024.109575. Online ahead of print.

Authors

Qiulu Li¹, Kaixin Ping¹, Yannan Xiang¹, Ying Sun¹, Zunhan Hu¹, Shujuan Liu¹, Xinying Guan², Mian Fu³

Affiliations

¹ Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, 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 Science and Technology Department, The First People's Hospital of Lianyungang, Lianyungang, 222000, China. Electronic address: 47431298@qq.com.
³ Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, 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; Jiangsu Institute of Marine Resources Development, Lianyungang, 222005, China. Electronic address: fumian@mail.nankai.edu.cn.

PMID: 38663463
DOI: 10.1016/j.fsi.2024.109575

Abstract

Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 μg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-β1 and il-10, while significantly down-regulated the gene expression levels of tnf-α, il-6 and il-1β. These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.

Keywords: Apoptosis; Avermectin; Ferulic acid; Inflammation; Kidney; Oxidative stress.