Reversal of aminopterin toxicity by water-soluble cupridihydroporphyrins (Chloresium)

Summary

Ingestion of 2 mg. per kilo per day of water-soluble cupri-chlorophyllins (Chloresium) protected weanling rats on a milk diet from aminopterin toxicity in each of seven experimental series. Similar protection was observed in one series of rats on a standard laboratory diet and in one series on laboratory diet supplemented with fresh greens.

In a single screening series, some protection of aminopterin-poisoned rats on a milk diet was forthcoming from administration of terramycin at 2 mg. per kilo per day, from Renshaw’s mammalian intestinal mucosa extract and from the parenteral administration of human plasma cholinesterase. Coprogen did not prolong survival under present experimental conditions. Availability of iron for hemoglobin synthesis from ferri-dihydroporphyrin (ferri-chlorophyllin) where the iron is chelated, in aminopterin-poisoned weanling rats on a milk diet, was not demonstrated.

The mechanism of chlorophyllin abrogation of aminopterin toxicity is analyzed. It is concluded that this does not result from chemical inactivation of aminopterin in vitro or in vivo. It may act as a formyl donor. However, chlorophyllin may also act by reversion of the fecal flora of ingesting animals in the same way as do other APF substances (mycin antibiotics, 11-oxysteroids and unidentified factors found in streptomyces fermentation residues).

The findings are presented because of the serious toxicity limitations of folic-acids in neoplastic disease. While their clinical use is probably on the wane, as long as they are so used, any knowledge of their counteraction is of clinical interest.