Hemolytic drugs aniline and dapsone induce iron release in erythrocytes and increase the free iron pool in spleen and liver

Incubation of rat erythrocytes with the hydroxylated metabolites of aniline and dapsone (4-4'-diaminodiphenylsulfone), phenylhydroxylamine and dapsone hydroxylamine, respectively, induced marked release of iron and methemoglo bin formation. On the contrary, no release of iron nor methemoglobin format ion was seen when the erythrocytes were incubated with the parent compounds (aniline and dapsone). The acute intoxication of rats with aniline or daps one induced a marked increase in the erythrocyte content of free iron and m ethemoglobin, indicating that the xenobiotics are effective only after biot ransformation to toxic metabolites in vivo. Prolonged administration of ani line or dapsone to rats produced continuos release of iron from erythrocyte s. Marked iron overload was seen in the spleen and in the liver Kupffer cel ls, as detected histochemically. The spleen weight in these subchronically treated animals was significantly increased. The free iron pool was markedl y increased in the spleen and to a lower extent in the liver. The possible relationships between iron release in erythrocytes, oxidative damage seen i n senescent cells, hemolysis, overwhelmed capacity of spleen and liver to k eep iron in storage forms and subsequent increase in low molecular weight, catalitically active iron is discussed. (C) 1999 Elsevier Science Ireland L td. All rights reserved.