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.