Astragaloside IV can mitigate heat stress-induced tissue damage through modulation of the Keap1-Nrf2 signaling pathway in grass carp (Ctenopharyngodon idella).

This study investigated the potential protective effect of AS-IV against heat stress-induced tissue damage in grass carp (Ctenopharyngodon idella). Grass carp were injected intraperitoneally with 0, 2, 4, and 8 mg/kg of AS-IV for three consecutive days, and then subjected to heat stress (35 ± 0.5 °C); thereafter, histopathological analyses of the liver and spleen were performed at 0, 6, 24, and 48 h, respectively. The results indicated that sustained heat stress resulted in hemorrhage, vacuolization, increased hepatic blood sinusoidal space, inflammatory cell infiltration in the liver, and decreased number of melanomacrophage centers in the spleen; conversely, 4 and 8 mg/kg AS-IV attenuated the pathological symptoms induced by heat stress and mitigated tissue damage in the liver and spleen of grass carp. The possible mechanism is that AS-IV promotes Nrf2 signaling through the downregulation of keap1a and keap1b, thereby activating the Keap1-Nrf2 signaling pathway, leading to changes in the levels of protection-related genes in the liver (GSH-Px and CAT levels were elevated while MDA levels were decreased, and gsh-px, cat, cu-zn sod, and hsp70 mRNA levels were upregulated while il-6 mRNA levels were downregulated) and spleen (GSH-Px, CAT, SOD, and GSH levels were increased while MDA levels were decreased, and il-6 mRNA levels were downregulated), which, in turn, improves the antioxidant ability of grass carp. Additionally, an appropriate dose of AS-IV transiently increased complement C3 levels after sustained heat stress, thereby improving the immunity of grass carp under heat stress. In conclusion, AS-IV can mitigate tissue damage induced in response to heat stress by modulating the redox homeostasis of grass carp and can be practically implemented in aquaculture sector.