T-2 toxemia and brain prostaglandins

T-2 toxin is a trichothecene mycotoxin which is a member of a family of closely related sesquiterpenoids. It was recently shown that T-2 toxemia is associated with elevated plasma levels of eicosanoids. To study further the effect of T-2 on the cyclooxygenase pathway of arachidonate we examined the release of PGE₂, TXB₂ and 6-keto-PGF_1α from brian tissue exposed to T-2 toxin in vivo or in vitro. Administration of T-2 toxin (0.75 or 2 mg/kg) to conscious rats caused a transient increase in the rate of the release of 6-kto-PGF_1α and TXB₂ from brain slices taken from the cortex (C); no effect was found in the hypothalamus (HT) or the nucleus tractus solitarius (NTS) region of the medulla oblogata. PGE₂ showed time and dose related increments (over 5 folds) in both the C and Ht but not in the NTS. Incubation of cortical or hypothalamic slices in oxygenated Krebs buffer with a wide range of T-2 toxin concentrations (10^-9-10^-3 M) demonstrated a complex repsonse: stimulation of PGE₂ and TXB₂ release from C slices at 10^-7 M (>40%, p<0.01 and 20%, p<0.05, respectively) and inhibition at high concentrations (>10^-4 M) of all PGs studied. Hypothalamic slices showed decrease in all PGs released by very low (10^-9-10^-8) or very high (10^-4 M) concentrations of T-2. These studies are consistent with the possibility that the arachidonate cascade in the central nervous system might have a role in the pathophysiology of trichothecene mycotoxicosis.