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 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.
Srivastava
P
P
Division of Biochemistry, Division of Pharmaceutics, Division of Microbiology, Central Drug Research Institute, Chattar Manzil Palace, Lucknow-1, India.
Singh
S
S
Jain
G K
GK
Puri
S K
SK
Pandey
V C
VC
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000634:Aminoquinolines / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000633:toxicity*; D037621:Artemisinins; D002474:Cell-Free System; D002738:Chloroquine / Q000008:administration & dosage / Q000633:toxicity; D042966:Cytochrome-B(5) Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D008253:Macaca mulatta; D008706:Methemoglobin / Q000187:drug effects* / Q000378:metabolism; D008708:Methemoglobinemia / Q000139:chemically induced* / Q000378:metabolism; D009115:Muridae; D010108:Oxyhemoglobins / Q000378:metabolism; D011319:Primaquine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D051381:Rats; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000633:toxicity
D000634:Aminoquinolines; D000962:Antimalarials; D037621:Artemisinins; D010108:Oxyhemoglobins; D012717:Sesquiterpenes; D002738:Chloroquine; D008706:Methemoglobin; C031327:artemisinin; D042966:Cytochrome-B(5) Reductase; D011319:Primaquine; C063469:bulaquine