Effects of sodium monofluoroacetate on glucose, amino-acid, and fatty-acid metabolism and risk assessment of glucose supplementation.
Sodium monofluoroacetate (SMFA; also known as compound 1080) is a highly toxic chemical; therefore, accidental exposure and intentional misuse are of great concern. SMFA intoxication is reportedly caused by the inhibition of aconitase. However, the pathogenesis underlying SMFA intoxication is not clear. This study was conducted to elucidate the acute effects of SMFA on glucose, amino-acid, and fatty-acid metabolism and to assess glucose supplementation as a possible alleviator or aggravator in SMFA intoxication. Rats were assigned to three groups: SMFA+saline, SMFA+glucose, and control (i.e., no SMFA), and blood samples were analyzed at 3 hours after SMFA or saline (control) administration. Additional rats were used for the monitoring of blood-glucose and lactate concentrations for 10 hour- and 14-day survival rates. SMFA increased the serum-citrate, serum-pyruvate, and blood-lactate concentrations. However, despite significant increases in these parameters when SMFA was administered with glucose, the effects on pH values were small and the survival rate was not changed. SMFA also increased the serum concentrations of free fatty acids, branched-chain amino acids, ammonia, urea, and calcium. The presence of glucose enhanced or suppressed these metabolic changes. Amphibolic intermediates in the tricarboxylic acid cycle might be supplied through the catabolism of proteins in SMFA intoxication. We conclude that other factors, in addition to the accumulation of lactate, citrate, and pyruvate, may affect survival rates, and that SMFA induces imbalances in glucose, amino-acid, and, fatty-acid metabolism. All these changes are inter-related and may contribute to SMFA intoxication.
Department of Hygiene and Public Health, Osaka Medical College, Osaka, Japan. hyg033@art.osaka-med.ac.jp
Hiroshi
H
Tsuji
Hiroyasu
H
Shimizu
Tomotaro
T
Dote
Kan
K
Usuda
Masafumi
M
Imanishi
Eri
E
Tanida
Keiichi
K
Fujimoto
Eisuke
E
Furuya
Koichi
K
Kono
D000596:Amino Acids / Q000097:blood*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D056890:Eukaryota; D005227:Fatty Acids / Q000097:blood*; D005463:Fluoroacetates / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D008297:Male; D009026:Mortality; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment
D000596:Amino Acids; D001786:Blood Glucose; D005227:Fatty Acids; D005463:Fluoroacetates; C014815:fluoroacetic acid; D005947:Glucose