New perspectives on lycopene: alleviation of sulfamethoxazole-induced inflammation, ER stress, and autophagy in the gills of grass carp.

Abstract

Sulfamethoxazole (SMZ), a sulfonamide antibiotic widely used in aquaculture, and its metabolites are released into the environment, becoming a potential threat to the health of hydrobionts. Lycopene (LYC), a potent antioxidant, was studied and found to possess anti-inflammatory and anti-oxidative stress pharmacological activities. This study aims to explore the potential protective effect of LYC on SMZ-induced gill injury in grass carp and its mechanism. The grass carp were exposed to 0.3 μg/L SMZ and 10 mg/kg body weight of LYC for 30 days. Fish gills were collected for examination of microstructure, oxidative stress indicators, and expression of related proteins. Our study found that SMZ exposure caused oxidative stress in fish gill tissues, with microstructural alterations. Meanwhile, relevant indicators of inflammation, such as IL-1β and NF-κB, were significantly up-regulated compared with the Con group, creating an inflammatory environment in vivo. In addition, SMZ also activated ER stress-related proteins and autophagy marker proteins. The above toxic effects were significantly alleviated after LYC intervention, and the mechanism involved LYC activating the Nrf2 pathway by binding to Keap1, upregulating HO-1 and NQO1 to enhance antioxidant capacity, and inhibiting NF-κB-induced inflammatory response. In conclusion, our study demonstrated that LYC as a dietary supplement could alleviate SMZ-induced damage in fish gills, and this natural antioxidant is expected to be developed into an effective drug to reduce the harm caused by SMZ in aquaculture.