Glutathione mitigates hypoxia stress-induced liver injury in juvenile grass carp (Ctenopharyngodon idellus) by alleviating mitochondrial dysfunction and autophagy

Hypoxia is a prevalent phenomenon in aquaculture, threatening the survival and growth of fish. The present study investigated the effects of dietary glutathione on hepatopancreatic injury in juvenile grass carp under hypoxia stress and its possible mechanisms. We formulated six diets with different levels of glutathione (0.00, 145.95, 291.90, 437.85, 583.80 and 729.75 mg/kg) to feed juvenile grass carp with initial body weights (11.08 +/- 0.01 g) for 70 days, followed by a 96-h hypoxia stress experiment. The results of this study showed that glutathione improved the growth performance of juvenile grass carp and alleviated hypoxia-induced glutathione depletion (GSH and GCL). In addition, glutathione decreased serum GPT and GOT activities and reduced ROS, MDA and PC contents in the hepatopancreas to attenuate tissue oxidative damage. Moreover, glutathione alleviated hypoxia stress-induced hepatopancreatic mitochondrial dysfunction, which may be related to the enhancement of mitochondrial oxidative phosphorylation and improvement of the mitochondrial quality control system. Furthermore, the ability of glutathione to alleviate hypoxia-induced hepatopancreatic autophagy may be associated with the inhibition of autophagy initiation, nucleation, elongation and degradation phases. In conclusion, glutathione attenuated hypoxia stress-induced hepatopancreatic injury in fish, which may be related to the fact that glutathione attenuated mitochondrial dysfunction and autophagy. Using the SGR from growth experiment and serum GPT activity under hypoxia stress as markers, it was determined that the optimum levels of glutathione to be added to juvenile grass carp for growth and against hypoxia stress were 451.50 mg/kg and 437.88 mg/kg, respectively.