Effects of drugs and metabolic inhibitors on the acute toxicity of T-2 toxin in mice.
The antidotal effects of antiinflammatory agents, inhibitors of bioamine syntheses, an opioid antagonist and other pharmacological agents on lethal toxicity, leukocytosis and ear inflammation, were investigated in mice subcutaneously administered or topically exposed to T-2 toxin, a trichothecene mycotoxin of Fusarium species. The acute lethal toxicity of T-2 toxin was reduced by administration of the steroidal anti-inflammatory agents, prednisolone and dexamethasone, and prolongation of survival times was demonstrated with an antihistaminic agent, diphenhydramine, and an opioid antagonist, naloxone. Prednisolone also antagonized leukocytosis and the increment of ear weight caused by T-2 toxin. These findings suggest that the action site(s) of steroidal anti-inflammatory agents is involved in the development of the toxic actions of T-2 toxin, and the implications of the results with bioamines and opioids are also discussed.
Ryu
J C
JC
Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Shiraki
N
N
Ueno
Y
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007928:Lethal Dose 50; D007964:Leukocytosis / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D012717:Sesquiterpenes / Q000037:antagonists & inhibitors*; D013605:T-2 Toxin / Q000037:antagonists & inhibitors* / Q000633:toxicity
D000893:Anti-Inflammatory Agents; D000963:Antimetabolites; D012717:Sesquiterpenes; D009270:Naloxone; D003907:Dexamethasone; D011239:Prednisolone; D013605:T-2 Toxin