Subject(s)
Imidazoles/isolation & purification , Immunosuppressive Agents/isolation & purification , Niridazole/urine , Thiocarbamates/isolation & purification , Animals , Chemical Phenomena , Chemistry , Chromatography, High Pressure Liquid , Humans , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Immunosuppressive Agents/chemical synthesis , Magnetic Resonance Spectroscopy , Male , Mass Spectrometry , Mice , Spectrophotometry , Thiocarbamates/chemical synthesis , Thiocarbamates/pharmacologyABSTRACT
It has been suggested that the suppression of cell-mediated immune phenomena following niridazole administration is most likely due to a niridazole metabolite rather than the parent drug. This hypothesis was tested using two inbred strains of mice that manifest different rates of microsomal niridazole oxidation and reduction. DBA/2J mice were found to metabolize niridazole at a rate approximately 3-fold greater than C57BL/6J mice under both aerobic and anaerobic conditions. Niridazole was found to be more potent with respect to suppression of cutaneous delayed hypersensitivity in the former than in the latter. An immunosuppressive component was isolated from the urine fraction obtained from niridazole-treated rats. This component was found to be chromatographically pure; have a simple UV absorbance spectrum containing no 360 nm absorbing material characteristic of niridazole; to show no strain difference with respect to potency or efficacy in the ear-swelling assay for cutaneous delayed hypersensitivity; and to be 10(7) times more potent than niridazole with respect to the suppression of cutaneous delayed hypersensitivity.
Subject(s)
Biological Products/pharmacology , Hypersensitivity, Delayed/drug therapy , Mice, Inbred C57BL/metabolism , Mice, Inbred DBA/metabolism , Niridazole/pharmacology , Animals , Biological Products/urine , Humans , Immune Tolerance , Male , Mice , Microsomes, Liver/metabolism , Niridazole/metabolism , Niridazole/urine , RatsABSTRACT
Urine dialysate from rats treated orally with 25 mg/Kg 3H-labeled niridazole was fractionated by DEAE-Sepharose column chromatography and was found to contain three radioactive metabolites and no parent compound. When human niridazole urine dialysate (NUD) was fractionated under identical conditions, fractions corresponding to the three rat NUD metabolites were found to inhibit the human one-way MLR. No inhibition was obtained with fractionated control urine dialysate. It was concluded that nonimmunosuppressive niridazole is metabolized by rats and man to produce three active compounds with the ability to suppress the in vitro response to alloantigens.
Subject(s)
Niridazole/pharmacology , Animals , Chemical Fractionation , Chromatography, Ion Exchange , Dialysis , Humans , Immunosuppression Therapy , Lymphocyte Culture Test, Mixed , Niridazole/metabolism , Niridazole/urine , RatsABSTRACT
After humans were treated at therapeutic doses with the trichomonacide metronidazole (Flagyl) and the antischistosomal agent niridazole mutagenic activity was demonstrable in their urines when tested with the histidine auxotroph of Salmonella typhimurium. Both compounds were active in the host-mediated assay in mice, and evidence of activity was found in the blood and urine of mice treated with niridazole but not with metronidazole.
