Alleviation of hypoxia stress induced oxidative damage, endoplasmic reticulum stress (ERS) and autophagy in grass carp (Ctenopharyngodon idellu) by TTO (Melaleuca alternifolia essential oil)

Because fish is a vital protein source, fish products are strongly linked to the health of humans. However, the survival of fish is seriously threatened by environmental hypoxia. The present study reported that an additive named tea tree oil (TTO) can prevent damage to the grass carp gill from hypoxia stress. The fish was fed with six graded levels of TTO (0, 40, 80, 120, 160, and 200 mg/kg) diets for 60 days and afterward subjected to a 96-h hypoxia stress trial. Our research elaborated that TTO alleviated the deterioration of serum parameters (cortisol, glucose, lactic dehydrogenase, and lactic acid) and reduced oxidative damage to the gills and apoptosis caused by hypoxia stress, thereby improving the structural integrity of the gills. In addition, TTO relieved gill endoplasmic reticulum stress (ERS), which could be associated with reduced levels of glucose-regulated protein 78 (GRP78) protein and activating its downstream pathways. Furthermore, TTO decreased the levels of LC3-II protein and the related ATG mRNA, suggesting that gill autophagy was suppressed and was probably related to the HIF–BNIP3 pathway. In summary, TTO reduced gill damage caused by hypoxia stress via reducing oxidative damage, endoplasmic reticulum stress (ERS), and autophagy in fish, implying TTO mitigated the negative effects of hypoxia. Based on oxidative damage biomarkers reactive oxygen species (ROS) and malonaldehyde (MDA) contents in the gills, the optimal addictive TTO concentration of grass carp was determined as 89.63 and 90.25 mg/kg, respectively. • Hypoxia stress caused gill damage in fish. • TTO reduced oxidative damage, apoptosis, ERS, and autophagy in grass carp gills. • TTO may inhibit PERK/eIF2α/ATF4, IRE1/XBP1, and ATF6 pathways to relieve ERS. • TTO reduced autophagy may be associated with inhibiting HIF/BNIP3 pathway.