High molecular weight hyaluronic acid improves salinity tolerance of Nile tilapia (Oreochromis niloticus) by mitigating apoptosis, alleviating oxidative stress and regulating carbohydrate metabolism

Salinity elevation induces hyperosmotic stress in fish, consistently triggering apoptosis. Apoptosis is recognized as the most sensitive indicator for assessing acute or severe salinity stress. Reducing the apoptosis under salinity stress may improve salinity tolerance of fish. Cells showed a significant decrease of hyaluronic acid content under hyperosmotic stress, suggesting that hyaluronic acid may play an important role in salinity adaptation. To investigate the functions and mechanisms by hyaluronic acid participating in osmoregulation, we explored in vitro and in vivo experiments separately. In vitro screening experiments, 100 μg/ml high molecular weight hyaluronic acid (HMW-HA, molecular weight = 1600 kDa) significantly improved cell survival rate under salinity stress. The HMW-HA scavenged ROS, enhanced cellular antioxidant capacity and inhibited apoptosis via the BCL2/caspase3 pathway. In the in vivo experiment, intraperitoneal injection of 90 mg/kg HMW-HA reduced the mortality rate of Nile tilapia (Oreochromis niloticus) under acute salinity stress. In addition to inhibiting apoptosis and improving antioxidant capacity, HMW-HA also enhanced glycolysis to produce more glucose, pyruvate and ATP for osmoregulation energy supplement Further, HMW-HA affected serum ion levels, while it had no significant effect on ion content in gills. HMW-HA alleviated gill damage such as gill filament disorder and inflammatory cell infiltration caused by high salinity. In summary, HMW-HA can enhance salinity tolerance of tilapia by inhibiting apoptosis, alleviating oxidative stress, and enhancing carbohydrate metabolism.