# Glutathione mitigates hypoxia-induced gill damage in juvenile grass carp (Ctenopharyngodon idellus) by alleviating endoplasmic reticulum stress and autophagy

## TL;DR

Glutathione helps protect the gills of young grass carp from damage caused by low oxygen levels by reducing stress in cells and improving antioxidant defenses.

## Contribution

This study is the first to show that glutathione mitigates hypoxia-induced gill damage in fish by alleviating endoplasmic reticulum stress and autophagy.

## Key findings

- Glutathione improves growth and antioxidant capacity in juvenile grass carp under hypoxia.
- Glutathione reduces gill tissue damage and apoptosis caused by hypoxia.
- Glutathione inhibits autophagy and endoplasmic reticulum stress in gill tissues under hypoxia.

## Abstract

Environmental hypoxia is a common phenomenon in aquaculture, which causes gill tissue injury in fish. Glutathione (GSH) is a vital antioxidant in animal tissues, and its levels decrease under hypoxic conditions. However, the effects of glutathione on fish under hypoxic stress remain poorly understood. This study aimed to investigate the impact of glutathione on gill tissue damage in fish under hypoxic stress and explore the underlying mechanisms.

Six experimental diets with varying glutathione concentrations. The actual glutathione levels in these diets, measured by high-performance liquid chromatography, were 0.00, 145.95, 291.90, 437.85, 583.80, and 729.75 mg/kg, respectively. Fish were fed these diets for 70 d, after which a 96-h hypoxic stress experiment was conducted. The experiment was set up with normoxic and hypoxic groups, in which the dissolved oxygen in the group was 6 mg/L, and that in the group was 1 mg/L.

This research revealed that glutathione could enhance the growth performance and antioxidant capability of juvenile grass carp while mitigating the structural damage to gill tissues induced by hypoxia stress. Mechanistic investigations further indicated that glutathione mitigated hypoxia-induced oxidative injury in gill tissues and improved their antioxidant capacity. In addition, glutathione attenuated gill apoptosis induced by hypoxia stress. Glutathione also inhibited the initiation, nucleation, elongation, and degradation phases of autophagy, thereby attenuating hypoxia-induced gill autophagy. Moreover, glutathione was found to alleviate hypoxia-induced endoplasmic reticulum stress (ERS) in gills, a response potentially linked to the suppression of PERK, IRE1, and ATF6 signaling pathways. Finally, based on the ROS and PC contents in gill tissue, the optimum glutathione supplementation levels for juvenile grass carp under hypoxia stress were 437.10 and 495.00 mg/kg, respectively.

In conclusion, our experimental results demonstrated the effectiveness of glutathione in alleviating gill tissue damage caused by hypoxic stress. This study confirms the feasibility and effectiveness of dietary glutathione addition to alleviate hypoxic stress in fish.

The online version contains supplementary material available at 10.1186/s40104-025-01274-x.