Acute ammonia toxicity and the protective effects of methionine sulfoximine on the swamp eel, Monopterus albus

Abstract

The objectives of this study were to examine how the swamp eel, Monopterus albus, defended against acute ammonia toxicity derived from the intraperitoneal injection with a sublethal dose (10 μmolg-1 fish) of ammonium acetate (CH3COONH4) followed by 24hr of emersion, and to elucidate the mechanisms of acute ammonia toxicity with respect to glutamine accumulation in the brain using L-methionine S-sulfoximine [MSO; a glutamine synthetase inhibitor]. When confronted with a sublethal dose of CH3COONH4 followed by emersion, only a small fraction of the exogenous ammonia was excreted, and ammonia contents in various organs, especially the brain, increased transiently to high levels. Increased glutamine synthesis and decreased amino acid catabolism in and outside the brain were involved in the defence against acute ammonia toxicity. When injected with a lethal dose (16 μmolg -1 fish) of CH3COONH4 followed by emersion, ammonia (~30 μmolg-1 tissue), but not glutamine (~5 μmolg-1 tissue), accumulated to extraordinarily high levels in the brain of succumbed fish. Hence, glutamine accumulation in the brain might not be the major mechanism of acute ammonia toxicity in M. albus. MSO (100 μgg-1 fish) had a partial protective effect in fish injected with a lethal dose of CH3COONH4. However, this effect was unrelated to the suppression of glutamine synthesis and accumulation in the brain. Instead, MSO suppressed the rate of ammonia buildup in the brain, possibly through its effects on glutamate dehydrogenase therein. © 2009 Wiley-Liss, Inc.