Hypoxia induces pyroptosis and inflammation in the liver of fat greenling (Hexagrammos otakii)

Abstract

In fisheries, hypoxia stress is one of the most common environmental stresses that often cause significant harm and losses to the aquaculture industry. The liver is the most important metabolic organ of the body, which is involved in energy metabolism, synthesizes various physiologically active substances, and is an important target organ for hypoxia in fish. This study investigated how acute hypoxia stress induces liver injury and mortality of Hexagrammos otakii. During the hypoxia treatment, reactive oxygen species (ROS), a metabolic intermediary made by the mitochondrial respiratory chain, are highly accumulated, the level of lipid peroxidation increased significantly in the liver tissue. The vacuolation of liver histiocyte is enhanced due to hypoxia. The downstream gene hypoxia-inducible factor (HIF)-1 can react to the elevated ROS in liver tissue. HIF-1α expression levels greatly increase when hypoxia is applied, which prompts the activation of the nlrp3/caspase-1/il-1β and caspase-3/gsdme pathway and encourages the inflammation and pyroptosis of the liver. After reoxygenation, nlrp3/caspase-1/il-1β pathway are reactivated and cause liver damage in H. otakii. In conclusion, it has been shown that hypoxia-stress modulates the expression of HIF-1 through an increase in ROS production, which then encourages the activation of the nlrp3/caspase-1/il-1β and caspase-3/gsdme pathway to cause liver injury. This research sheds fresh light on the mechanism of hypoxia-induced pyroptosis and demonstrates the usefulness of the ROS-HIF-1 signaling pathway as a possible therapeutic target to halt the progression of hypoxia-induced illnesses.