A Simple and Rapid Evaluation of Methemoglobin Toxicity of 8-Aminoquinolines and Related Compounds

• Published in: Ecotoxicology and environmental safety Vol. 45; no. 3; pp. 236 - 239
• Main Authors: Srivastava, Pratima, Singh, S., Jain, G.K., Puri, S.K., Pandey, V.C.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.03.2000; Elsevier
• Subjects: 8-Aminoquinoline; 8-aminoquinolines; 80/53; Administration, Cutaneous; Administration, Oral; Aminoquinolines - administration & dosage; Aminoquinolines - toxicity; Animals; antimalarial; Antimalarials - administration & dosage; Antimalarials - toxicity; Artemisinins; Biological and medical sciences; Cell-Free System; Chloroquine - administration & dosage; Chloroquine - toxicity; Cytochrome-B Reductase - antagonists & inhibitors; Cytochrome-B Reductase - metabolism; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Erythrocytes - drug effects; Erythrocytes - metabolism; Macaca mulatta; Mastomys; Medical sciences; methemoglobin; Methemoglobin - drug effects; Methemoglobin - metabolism; Methemoglobinemia - chemically induced; Methemoglobinemia - metabolism; Muridae; oxyhemoglobin; Oxyhemoglobins - metabolism; Pharmacology. Drug treatments; primaquine; Primaquine - administration & dosage; Primaquine - analogs & derivatives; Primaquine - toxicity; Rats; Sesquiterpenes - administration & dosage; Sesquiterpenes - toxicity; Toxicity: blood; transdermal tape; 8-aminoquinolines; primaquine; Mastomys; transdermal tape; methemoglobin; antimalarial; 80/53; Antimalarial; Evaluation; Animal model; Methodology; Enzyme; Primaquine; Toxicity; Rodentia; Macaca mulatta; Methemoglobin; Percutaneous route; Antiprotozoal agent; reductase; Vertebrata; Rapid technique; Mammalia; Enzymatic activity; Primates; Simioidea; Oxidoreductases; Inhibition; Rattus rattus; Simplicity; Cytochrome-b
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1006/eesa.1999.1868

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.