The LD50 of Methotrexate (Nsc-740) by the Oral Route in Unilaterally Nephrectomized, Sham Operated and Normal Mice

摘要

The object of this study was to determine whether Methotrexate (NSC-740) has greater toxicity in unilaterally nephrectomized animals. For this purpose the LD50 of the compound was determined by the oral route in unilaterally nephrectomized, sham operated and normal mice. According to the results of this experiment, nephrectomy does not alter the LD50 value of NSC-740; but this experiment is not definitive. The lowest LD50 of 251 mg/kg obtained with the nephrectomized male mice was not significantly different than that obtained with the control males, 279 mg/kg; but the control males were not from the original batch of animals, although they were presumably from the same stock and of the same age. On the other hand the LD50 for the sham operated animals is signficantly higher than the LD50 for the nephrectomized groups; but there is a good possibility that this high value is aberrant due to poor absorption of the compound from the gastrointestinal tract at high dose levels. So the possibility remains that there is a real biological effect which can be demonstrated with male animals at the proper stage of the post-nephrectomy period and with a route of administration other than oral. (Author)