Irritancy of cyclophosphamide-derived aldehydes (Acrolein, Chloracetaldehyde) and their effect on lymphocyte distribution in vivo: Protective effect of thiols and bisulphite ions

Abstract

A strategy is described for investigating agents such asN-acetylcysteine or penicillamine that might be used as adjuvant therapy with cyclophosphamide, to lessen the toxic side-effects of this latter drug caused by some of its metabolites. The toxic effects of acrolein and chloracetaldehyde were determined by (a) their effects on lymphocyte circulation and (b) their oedemagenic activity in rats. Stable thiols and bisulphite ions antagonised this aldehyde toxicity/irritancy; thiosulphate ions did not. Thiosulphate and bisulphite ions antagonised the irritancy/toxicity of a mustard, mechlorethamine (HN-2). The possible relationship of intrinsic irritancy to anti-inflammatory activity is discussed briefly.