Acute ammonia toxicity and the protective effects of methionine sulfoximine on the swamp eel, Monopterus albus.
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 micromol g(-1) fish) of ammonium acetate (CH(3)COONH(4)) followed by 24 hr 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 CH(3)COONH(4) 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 micromol g(-1) fish) of CH(3)COONH(4) followed by emersion, ammonia (approximately 30 micromol g(-1) tissue), but not glutamine ( approximately 5 micromol g(-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 microg g(-1) fish) had a partial protective effect in fish injected with a lethal dose of CH(3)COONH(4). 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.
Tng
Yvonne Y M
YY
Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
Chew
Shit F
SF
Wee
Nicklaus L J
NL
Wong
Fung K
FK
Wong
Wai P
WP
Tok
Chia Y
CY
Ip
Yuen K
YK
D000085:Acetates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000208:Acute Disease; D000410:Alanine Transaminase / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000641:Ammonia / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008717:Methionine Sulfoximine / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D023701:Smegmamorpha; D014508:Urea / Q000032:analysis / Q000378:metabolism
D000085:Acetates; D000596:Amino Acids; D004791:Enzyme Inhibitors; D008717:Methionine Sulfoximine; D000641:Ammonia; D014508:Urea; D000410:Alanine Transaminase; D005974:Glutamate-Ammonia Ligase; C018824:ammonium acetate