A simple and rapid evaluation of methemoglobin toxicity of 8-aminoquinolines and related compounds

Methemoglobin, a toxic ferric form of hemoglobin, is continuously formed in normal erythrocytes, but during abnormal situations in situ, the level is enhanced. 8-Amino-quinolines and related compounds are causative agents for methemoglobin formation. Employing oxyhemoglobin, methemoglobin toxicity w as about six times higher with primaquine compared to CDRI Compound 80/53 a t 10(-9) M concentration. Methemoglobin reductase activity was also complet ely inhibited by primaquine, whereas 24% inhibition was noted in the case o f 80/53 at the same concentrations. Mastomys, a rodent animal model, was fo und to be equally good for comparative evaluation of methemoglobin toxicity . Further, with the use of primaquine transdermal tape on the Mastomys mode l, a rise in methemoglobin occurred with increase in time. In conclusion, t he study presents simple, economical, less time-consuming methods for the e valuation of methemoglobin toxicity, in vitro and in vivo, without employin g the conventional Beagle dog model. (C) 2000 Academic Press.