Toxicity of Anguidine in Mice

Toxicity of Anguidine in Mice. CONNER, M. W., DECAMARGO, J.,PUNYARIT, P., RIENGROPITAK, S., ROGERS, A. E., AND NEWBERNE,P. M. (1986). Fundam Appl Toxicol. 7, 153-164. A characteristicof the trichothecene mycotoxin, anguidine, is its extreme toxicityto organs with populations of rapidly dividing cells. In preparationfor evaluation of compounds that may protect against anguidinetoxicity, we measured the LD50 of anguidine administered bygastric gavage (ig) or intraperitoneal injection (ip) and studiedthe dose- and time-dependent effects of anguidine on lymphohematopoieticorgans, intestine, and testis, and measured hematocrit and peripheralblood leukocyte counts in male CD-I mice. The ig LD50 at 96hr was 15.5 mg/kg; after ip administration the LD50 at 96 hrwas 20.0 mg/kg. Characteristic changes caused by sublethal dosesof anguidine were cell depletion and necrosis in lymphohematopoieticorgans, multifocal necrosis of intestinal epithelium, and diffusenecrosis of germinal epithelium followed by progressive tubuledegeneration in the testes. There was leukocytosis due to bothlymphocytosis and neutro-philia in the first few hours followinganguidine exposure, followed by lymphopenia, neutropenia. andanemia by 3 days. After lethal doses, the intestinal necrosiswas transmural, and there was extensive necrosis of lymphohematopoieticorgans. There was rapid recovery after sublethal anguidine exposureof all anguidine-sensitive organs except for testis where decreasedweights and abnormal spermatogenesis persisted for the 2-weekobservation period. Our results suggest that intestinal necrosisis an important cause of death following anguidine exposure.Atrophy of seminiferous tubules may have some value as an indicatorof prior anguidine exposure, but the testicular changes arenot unique to this compound.