Environmentally relevant concentration of sulfamethoxazole-induced oxidative stress-cascaded damages in the intestine of grass carp and the therapeutic application of exogenous lycopene.

Abstract

Due to the unreasonable use and discharge of the aquaculture industry, over standard of the antibiotics has been frequent in different types of water environments, causing adverse effects on aquatic organisms. Lycopene (LYC) is an esculent carotenoid, which is considered to be a strong antioxidant. This study was designed to explore the therapeutic effect of LYC on antibiotic (sulfamethoxazole (SMZ)) induced intestinal injury in grass carp Ctenopharyngodon idella. The 120 carps (the control, LYC, SMZ, and co-administration groups) were treated for 30 days. We found that treatment with LYC significantly suppressed SMZ-induced intestinal epithelial cell damage and tight junction protein destruction through histopathological observation, transmission electron microscopy and detection of related genes (Claudin-1/3/4, Occludin and zonula occludens (ZO)-1/2). Furthermore, LYC mitigated SMZ-induced dysregulation of oxidative stress markers, including elevated malondialdehyde (MDA) levels, and consumed super oxide dimutese (SOD), catalase (CAT) activities and glutathione (GSH) content. In the same treatment, LYC reduced inflammation and apoptosis by a detectable change in pro-inflammatory factors (tumor necrosis factor-alpha (TNF-β), interleukin (IL)-1β, IL-6 and IL-8), anti-inflammatory factors (transforming growth factor-beta (TGF-β) and IL-10) and pro-apoptosis related genes (p53, p53 upregulated modulator of apoptosis (PUMA), Bax/Bcl-2 ratio, caspase-3/9). In addition, activation of autophagy (as indicated by increased autophagy-related genes through AMPK/ATK/MTOR signaling pathway) under the stress of SMZ was also dropped back to the original levels by LYC co-administration. Collectively, our findings identified that LYC can serve as a protectant agent against SMZ-induced intestinal injury.