The Role of Oxidative Stress in the Mechanisms of Ammonia-Induced Brain Swelling and Tolerance in the Goldfish (Carassius auratus)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in teleosts, in which blood ammonia concentrations can fluctuate markedly following feeding, exercise, and exposure to environmental ammonia. This study aimed to determine if exposure to high external ammonia (HEA; 5 mmol L-1) induced oxidative stress in the brain and liver of goldfish. HEA exposure led to 10-fold increases in internal ammonia and oxidative stress in the liver and brain. Oxidative damage was most pronounced in the brain, in which there were 114% increases in thiobarbituric-acid reactive substances (TBARS) and 3–fold increases in protein carbonyl content after 72 h HEA in warm-acclimated (14°C) goldfish. Notably, cold-water acclimation (4°C) completely attenuated the oxidative stress response in the goldfish brain and liver. This was accompanied by a marked diminution of the brain swelling response in cold-acclimated goldfish, whereas brain water volume increased by 20% in normothermic (14°C) individuals after 72 h HEA. The present study also demonstrated an increase in the activity of key antioxidant enzymes in the brain (CAT, GPx, GR) and liver (SOD, CAT, GR) during HEA, suggesting that goldfish are able to upregulate their antioxidant capacity in response to ammonia. In conclusion, oxidative stress appears to play a central role in the brain swelling process during acute hyperammonemia. Moreover, goldfish brains appear to have a high capacity to withstand oxidative stress in response to variations in internal ammonia. This likely explains why goldfish are more resilient to this homeostatic disturbance than mammalian brains