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-FGF1 alpha from brain 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-keto-PGF1 alpha 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 response: stimulation of PGE2 and TXB2 release from C slices at 10(-7) M (greater than 40%, p less than 0.01 and 20%, p less than 0.05, respectively) and inhibition at high concentrations (greater than 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.
Shohami
E
E
Feuerstein
G
G
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D015232:Dinoprostone; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000494:pharmacology*; D013605:T-2 Toxin / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D011453:Prostaglandins; D011458:Prostaglandins E; D012717:Sesquiterpenes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013605:T-2 Toxin; D015232:Dinoprostone