bulaquine and artemisinin

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 was about six times higher with primaquine compared to CDRI Compound 80/53 at 10(-9) M concentration. Methemoglobin reductase activity was also completely inhibited by primaquine, whereas 24% inhibition was noted in the case of 80/53 at the same concentrations. Mastomys, a rodent animal model, was found to be equally good for comparative evaluation of methemoglobin toxicity. Further, with the use of primaquine transdermal tape on the Mastomys model, a rise in methemoglobin occurred with increase in time. In conclusion, the study presents simple, economical, less time-consuming methods for the evaluation of methemoglobin toxicity, in vitro and in vivo, without employing the conventional Beagle dog model.

Topics: Administration, Cutaneous; Administration, Oral; Aminoquinolines; Animals; Antimalarials; Artemisinins; Cell-Free System; Chloroquine; Cytochrome-B(5) Reductase; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Erythrocytes; Macaca mulatta; Methemoglobin; Methemoglobinemia; Muridae; Oxyhemoglobins; Primaquine; Rats; Sesquiterpenes