Effects of radioprotective compounds and anti-inflammatory agents on the acute toxicity of trichothecenes.
Antidotic effects of radioprotective and anti-inflammatory drugs against the acute toxicity of T-2 toxin and fusarenon-X, the trichothecene mycotoxins of Fusarium species, were examined in mice and rats with two toxicological parameters, the lethal toxicity and the increment of intestinal fluid volume. The s.c. and i.v. LD50 values of T-2 in male 6-week-old mice were 2.1 and 3.8 mg/kg, respectively, and the s.c. LD50 in 4-week-old mice was 1.6 mg/kg. Pretreatment of mice with steroidal anti-inflammatory agents such as prednisolone and hydrocortisone resulted in a marked reduction in the lethal toxicity of T-2 toxin. However, pretreatment of mice with several radioprotective agents exhibited neither a prolongation of survival time nor a decrease in lethal toxicity in the mice. Enteropooling assay revealed that the steroidal anti-inflammatory drugs also depressed the trichothecene-induced increment of intestinal fluid volume in rats, while no significant effects were observed with non-steroidal inhibitors of the arachidonate cascade. In rats given fusarenon-X, the content of cyclic AMP in the mucosa of ileum was dose- and time-dependently increased, but its maximal increment was only 1.5-fold of the control value. These findings indicate an involvement of the action site of steroidal anti-inflammatory drugs in the development of acute toxicity of trichothecenes in rodents.
Mutoh
A
A
Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Ishii
K
K
Ueno
Y
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D006854:Hydrocortisone / Q000494:pharmacology; D007082:Ileum / Q000032:analysis; D007413:Intestinal Mucosa / Q000032:analysis; D007422:Intestines / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011239:Prednisolone / Q000494:pharmacology; D011458:Prostaglandins E / Q000032:analysis; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000633:toxicity*; D013605:T-2 Toxin / Q000633:toxicity*; D014255:Trichothecenes / Q000633:toxicity*
D000893:Anti-Inflammatory Agents; D011458:Prostaglandins E; D011837:Radiation-Protective Agents; D012717:Sesquiterpenes; D014255:Trichothecenes; C002469:fusarenon-X; D011239:Prednisolone; D000242:Cyclic AMP; D013605:T-2 Toxin; D015232:Dinoprostone; D003078:Colchicine; D006854:Hydrocortisone