Ferulic acid attenuated difenoconazole-induced immunotoxicity in carp by inhibiting TRAF/TAK1/NF-κB, Nrf2 and p53 pathways

Haoming Ma; Zihui Meng; Li Zhou; Huimiao Feng; Xinyu Wu; Yue Xin; Jingquan Dong; Yanan Li

doi:10.1016/j.ecoenv.2023.115339

Ferulic acid attenuated difenoconazole-induced immunotoxicity in carp by inhibiting TRAF/TAK1/NF-κB, Nrf2 and p53 pathways

Ecotoxicol Environ Saf. 2023 Aug 10:262:115339. doi: 10.1016/j.ecoenv.2023.115339. Online ahead of print.

Authors

Haoming Ma¹, Zihui Meng², Li Zhou², Huimiao Feng³, Xinyu Wu³, Yue Xin³, Jingquan Dong⁴, Yanan Li⁵

Affiliations

¹ Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang 222005, China; School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
² School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
³ Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang 222005, China.
⁴ Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang 222005, China. Electronic address: 2018000029@jou.edu.cn.
⁵ School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China. Electronic address: lyn1042310@163.com.

PMID: 37572622
DOI: 10.1016/j.ecoenv.2023.115339

Abstract

Difenoconazole (DFZ) is a classical triazole fungicide that causes immunosuppression in non-target organisms. Ferulic acid (FA) is a polyphenolic molecule found in nature that has antioxidant and anti-inflammatory activities. The purpose of this investigation was to see if FA could prevent DFZ-induced immunosuppression and to identify the potential mechanisms. Carp were exposed to 1/10 LC₅₀ of DFZ as well as fed normal feed or feed containing dietary additive FA for 30 d. It was found that DFZ-induced immunosuppression could be improved by FA, as evidenced by upregulation of Hb, C3 and IgM and downregulation of LDH. It was then investigated that FA could ameliorate DFZ-induced splenic injury through p53-mediated apoptosis. At the same time, enhancing the levels of CAT, GSH and T-AOC in spleen and transcription levels Nrf2 signaling pathway related genes indicated that FA reduced oxidative damage caused by DFZ by blocking the Nrf2 signaling pathway. In addition, FA inhibited the inflammatory response triggered by TRAF/TAK1/NF-κB signaling pathway, downregulated the transcript levels of pro-inflammatory factors (il-1β, tnf-α, il-6) and the level of NLRP3 inflammasome (NRLP3, ASC, Caspase 1), and upregulated the transcript levels of anti-inflammatory factors (tgf-β1, il-10). In conclusion, the above results suggested that FA mediated TRAF/TAK1/NF-κB, Nrf2, and p53 pathways to attenuate DFZ-induced inflammation, oxidative stress, and apoptosis thereby enhancing the immune capacity of carp.

Keywords: Apoptosis; Difenoconazole; Ferulic acid; Inflammation; Oxidative stress.