Acute hypoxia induces liver mitochondrial and endoplasmic reticulum stress in adult grass carp (Ctenopharyngodon idella): Palliative effects of vitamin A.

In aquaculture, hypoxia is a serious hazard that is frequently reduced by vitamin supplementation. Vitamin A (VA), which fish cannot produce on their own, is vital for their health, but the ability of VA to help fish fight hypoxic stress has not been reported. The study examined the impacts of VA on growth performance, hypoxia-induced liver injury, mitochondrial stress, and endoplasmic reticulum stress in adult grass carp (Ctenopharyngodon idella). Six hundred grass carp (726 ± 1.2 g; 441 d age) were divided into six groups with 4 replicates per group and 25 fish per replicate and fed six diets containing VA levels of 375, 862, 1614, 2099, 2786, and 3118 IU/kg for 60 d to determine growth performance, followed by a 96-h acute hypoxic stress experiment. The results showed that VA (1614-2786 IU/kg) increased final body weight (FBW), percentage weight gain (PWG), and feed efficiency (FE) (P < 0.05). Vitamin A (862-2786 IU/kg) also attenuated the levels of blood parameters (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and cortisol [Cor]) (P < 0.05) and the excessive accumulation of reactive oxygen species (ROS) (P < 0.001) induced by hypoxia. Furthermore, VA (2099-2786 IU/kg) increased the mRNA relative expression levels of mitochondrial biogenesis genes (SDHA, TFAM, PGC1α/β, and NRF1/2) (P < 0.05), while 1614 to 2099 IU/kg of VA decreased the mRNA relative expression levels of mitochondrial stress genes (LONP1, ClpP, Tom40, and FGF21) (P < 0.05), and VA at 1614 IU/kg decreased endoplasmic reticulum stress genes (GRP78, IRE1, XBP1, ATF6, PERK, eIF2α, and CHOP) (P < 0.05). Vitamin A (1614-2786 IU/kg) also enhanced the protein levels of SDHA (P = 0.045) and HSP60/70 (P = 0.001), and VA at 1614 IU/kg reduced the protein levels of FGF21 (P < 0.001), p-PERK (P = 0.002), and p-IRE1 (P < 0.001). In short, intermediate VA supplementation improved growth and alleviated hypoxia-induced mitochondrial and endoplasmic reticulum stress. Moreover, the optimal dietary VA levels for adult grass carp were determined to be 1921 IU/kg for growth (based on weight gain) and 2450 IU/kg for hypoxic stress resistance (based on AST).