Trichothecene mycotoxins, namely T-2 toxin and vomitoxin among others, are responsible for widespread occurrences of fatal toxicosis associated with the consumption of moldy grain by humans and animals. Vomiting (or emesis) is an invariable manifestation of the lethal syndrome said to resemble the pattern of high-energy radiation sickness. It has been conjectured but not proved that the mycotoxin-induced vomiting results from excitation of the medullary emetic chemoreceptor trigger zone (CTZ) discovered by Borison and Wang in 1950. The first of the present research objectives therefore is to test for the emetic responsiveness to selected trichothecene mycotoxins in cats subjected to chronic ablation of the area postrema which embodies the CTZ. If these operated animals are not then refractory to the emetic stimulus, a program of neurosurgical interventions is planned to identify the actual receptor site of action. The mycotoxins will be administered by systemic as well as intracerebroventricular routes of injection. The second objective of this proposal is to delineate precisely the cardiovascular and respiratory effects that characterize the acute shocklike state produced by the mycotoxins. This aspect of mycotoxin toxicology has remained relatively unexplored. All appropriate physiological laboratory measurements will be made on barbiturate-anesthetized or decerbrate unanesthetized cats. Specific variables to be observed are arterial blood pressure, heart rate, respiratory excursions, respiratory gases, blood gases and pH, and muscle and nerve action potentials as required. A variety of neurologic and pharmacodynamic maneuvers will be performed for a functional analysis of the toxic action affecting the vital homeostatic mechanisms. Analytic procedures include baro- and chemo-denervations, visceral afferent nerve interruptions, central electrolytic lesions and electrical stimulation of the cardiovascular and respiratory control centers. Emphasis will be given to a comparison of mycotoxin-induced dysfunctions with the pathophysiological effects of x-radiation presently under investigation in this laboratory.
| Borison, H L; Goodheart, M L; Thut, D C (1991) Hypovolemic shock in acute lethal T-2 mycotoxicosis. Toxicol Appl Pharmacol 108:107-13 |
| Gonsalves, S F; Landgraf, B E; Ciardelli, T L et al. (1991) Early toxicity of recombinant interleukin-2 in cats. Arch Int Pharmacodyn Ther 310:175-85 |
| Borison, H L; Goodheart, M L (1989) Neural factors in acute emetic, cardiovascular, and respiratory effects of T-2 toxin in cats. Toxicol Appl Pharmacol 101:399-413 |
