NITROXIDE STABLE RADICAL PREVENTS PRIMAQUINE-INDUCED LYSIS OF RED-BLOOD-CELL

Primaquine (PQ), an antimalarial drug, is known to produce multiple ox idative effects in red blood cells (RBC). Because H2O2, OH and intrace llular superoxide are implicated in this oxidation, the effect of cell -permeable nitroxide 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) capa ble of scavenging O-2(-) has been studied. PQ caused RBC lysis and fac ilitated the oxidation of oxyhemoglobin (oxyHb) to methemoglobin (MetH b). The lysis was partially inhibited by catalase and by the metal che lating agent 2,2-dipyridyl. TEMPO blocked PQ-induced RBC lysis in dose -dependent manner (2 mM IC50) but enhanced the oxidation of oxyHb to M etHb. PQ facilitated the lysis also in the presence of CO but without effecting Hb oxidation. This hemolysis, however, was inhibited by TEMP O. The results indicated that: (a) no causative relationship exists be tween PQ-induced Hb oxidation and RBC lysis; (b) TEMPO can directly ox idize heme-iron without causing membrane injury; (c) the aerobic toxic ity of PQ in this system is mediated by O-2(-) and H2O2 and possibly b y redox-active labile metals (d) TEMPO can protect by detoxifying O-2( -) and oxidizing reduced labile metal ions and thus blocking their par ticipation in Fenton reaction.