Induction of Haemolytic Anaemia by Substituted Phenylhydrazines

Abstract

The induction of anaemia and reticulocytosis by arylhydrazines was influenced by substituents on the benzene ring of phenylhydrazine. Arylhydrazines with ortho substituents, which would hinder the binding by haemoglobin of a ligand derived from the arylhydrazine, resulted in the least anaemia and reticulocytosis. These results are consistent with a previous finding that hydrazinobenzoic acid, which did not produce a ferrihaemochrome from ferrihaemoglobin, did not induce anaemia. The parallelism between the formation of a ferrihaemoglobin compound and the induction of anaemia supports the hypothesis that destabilization of haemoglobin by the binding of a ligand derived from the aryl portion of an arylhydrazine is an essential step in arylhydrazine-induced haemolytic anaemia.

Antioxidant and Vascular Protective Activities of Cratoxylum formosum, Syzygium gratum and Limnophila aromatica

“…It is well recognized that PHZ is a strong oxidant agent, which is used in laboratories to induce hemolytic anemia by oxidizing the alpha-globin chain of hemoglobin, and consequently, leads to enhanced erythropoietic activity, increased oxidative damage, and increased iron absorption and tissue iron overload. [31][32][33][34] The auto-oxidation of PHZ can generate various radicals such as O 2 ·Ϫ , hydroxyl radical, and a complex array of PHZderived radicals, i.e. phenylhydazyl radical, phenyldiazene and benzenediazonium ions.…”

The distribution and aggregatability of intramembrane particles in phenylhydrazine-treated human erythrocytes

“…On the other hand, two other Heinz-body-inducing drugs acetylphenylhydrazine and hydrazine caused similar fluorescence at 15 mM concentration. The latter finding indicates that the presence of phenyl group is not necessary for the oxidant-induced red cell fluorescence, Moreover, since hydroxylamine (which is also a potent Heinz-body-inducing agent) caused similar fluorescence at concentrations above 5 mM after 4 h of incubation, the possibility that the fluorescence is due to the reported interaction between methaemoglobin and oxidized phenylhydrazine, phenyldiazene [6,15,16] can also be excluded. It should be mentioned that similar autofluorescence of Heinz-body-containing erythrocytes has already been described in haemoglobin Kt~ln disease as well as in some other forms of unstable haemoglobin diseases [17,12].…”

A New Animal Model of Hemolytic Hyperbilirubinemia-Induced Bilirubin Encephalopathy (Kernicterus)

“…These results implicated oxidation products of PHZ and not proteolytic degradation as major contributors to PHZ-induced protein damage in red blood cells ghosts (28). PHZ directly oxidizes Hb and has a propensity to exacerbate G6PD deficiency and the precipitation of unstable hemoglobins (13). Hemolysis induced by PHZ has been used recently to increase bilirubin production in mice and investigate the role of MRP1 mediated ATP-dependent cellular extrusion of unconjugated bilirubin (29), and microarray technology has suggested potential biomarkers for PHZ-induced hemolytic anemia (30).…”

“…Hemolytic anemia from PHZ treatment is believed to result from destabilization of Hb by the binding of a ligand derived from the aryl portion of PHZ (13). Exposure of erythrocytes to PHZ results in the degradation of both monomers of spectrin, a major cytoskeleton membrane protein (27).…”

“…Our objective was to create a new model of hemolysisinduced acute bilirubin encephalopathy using phenylhydrazine (PHZ), which lyses red blood cells (13). We administered PHZ to jj Gunn rat pups who, similar to human neonates, have impaired conjugation of bilirubin.…”