Methylthiazolidine-4-carboxylate for treatment of acute T-2 toxin exposure.
The effect of T-2 toxin on hepatic glutathione content and the protective effect of 2-methyl-thiazolidine-4-carboxylate (MTCA), an L-cysteine prodrug, were studied in mice. Acute exposure to T-2 toxin (4 mg kg-1, s.c.) resulted in a progressive decrease in glutathione content, reaching a minimum 6-8 h after toxin administration. Because T-2 toxin caused decreased food consumption, a condition known to deplete hepatic glutathione, glutathione was measured in both fed and fasted control and toxin-treated mice. Glutathione content (mumol g-1 tissue) was 9.01 +/- 0.66 (control) and 4.26 +/- 0.41 (toxin) for fed mice, 4.45 +/- 0.39 (control) and 2.45 +/- 0.26 (toxin) for 16-h fasted mice, and 7.18 +/- 0.26 (control) and 3.76 +/- 0.65 (toxin) for mice fed before, but fasted after exposure to toxin. In all cases, toxin treatment resulted in significant decreases in glutathione content compared to controls. Treatment of T-2-intoxicated mice with MTCA (750 mg kg-1, i.p.) not only maintained glutathione content at control levels or higher but significantly improved survival as well. Therefore, the toxicity and lethality of T-2 toxin may be associated with decreased hepatic glutathione content, since MTCA maintained glutathione content and improved survival.
Fricke
R F
RF
US Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD 21701-5011.
Jorge
J
J
D000818:Animals; D000931:Antidotes; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005215:Fasting / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011355:Prodrugs / Q000627:therapeutic use*; D013605:T-2 Toxin / Q000037:antagonists & inhibitors* / Q000506:poisoning; D013844:Thiazoles / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects
D000931:Antidotes; D011355:Prodrugs; D013844:Thiazoles; C008499:2-methylthiazolidine-4-carboxylic acid; D005978:Glutathione; D013605:T-2 Toxin