| Summary: | Northern elephant seals (NES) are naturally exposed to prolonged fasting (2–3 mo) while weaning, molting or breeding. In terrestrial mammals, fasting increases reactive oxygen species (ROS) production and oxidative damage. Fasting in NES activates the renin‐angiotensin system and increases the expression of the ROS‐producing protein Nox4 without increasing local or systemic indices of oxidative damage. The mechanisms NES evolved to cope with fasting‐induced ROS production remain unexamined. To test our hypothesis that antioxidant enzymes and glutathione (GSH) increase with fasting in NES, muscle biopsies and blood samples were collected from early and late fasted NES pups (N= 17). Antioxidant enzymes (superoxide dismutases [SOD], catalase [CAT] and GSH peroxidase [GPx]) muscle protein expression, their muscle and red blood cell (RBC) activity levels, and muscle and RBC GSH content were analyzed. Fasting increased antioxidant enzymes expression (40–60%) as well as muscle and RBC SOD (6 ± 2 vs 12 ± 4 U/mg protein; 788 ± 16 vs 920 ± 24 U/mL), CAT (29 ± 4 vs 69 ± 15 U/mg protein; 5192 ± 753 vs 8185 ± 973 U/mL) and GPx activities (6 ± 1 vs 10 ± 0.5 U/mg protein; 430 ± 90 vs 935 ± 149 U/mL). Muscle (4 ± 1 vs 19 ± 4 nmol/mg protein) and RBC GSH (0.5 ± 0.09 vs 1.3 ± 0.3, μmol/g Hb) also increased with fasting suggesting that endogenous antioxidants contribute to NES tolerance to fasting‐induced ROS production. Moreover, the accumulation of antioxidants during the fast may prepare NES to cope with dive‐induced ROS production, since fasting precedes the beginning of their diving lifestyle. Funded by NIH HL091767.
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