Activated oxygen generation by a primaquine metabolite: inhibition by antioxidants derived from Chinese herbal remedies.
Primaquine is an important antimalarial drug which causes hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PDH) deficiency, probably due to oxidant generation by its metabolites. One of primaquine's metabolites, 5,6-dihydroxy-8-aminoquinoline (AQD), was found to cause chemiluminescence (CL) in vitro when incubated in the presence of luminol. This CL is inhibited by catalase and deferoxamine, unaffected by mannitol, and stimulated by superoxide dismutase (SOD), suggesting that it is mediated by H2O2. Three antioxidants (daphnetin, ferulate, and maltol), derived from Chinese herbal remedies, inhibited AQD- and H2O2-mediated CL, whereas a fourth, anisodamine, had no effect. Daphnetin also potently inhibited H2O2-mediated lipid peroxidation as measured by the production of thibarbituric acid reacting substances (TBARS). Thus, the possibility is raised that an antioxidant might be able to mitigate the oxidant hemolytic effects of primaquine.
Hong
Y L
YL
Department of Biochemistry, Peking Union Medical Center, Beijing, China.
Pan
H Z
HZ
Scott
M D
MD
Meshnick
S R
SR
D000634:Aminoquinolines / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007501:Iron / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D010084:Oxidation-Reduction; D010100:Oxygen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011319:Primaquine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013858:Thiobarbiturates / Q000378:metabolism
D000634:Aminoquinolines; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D005609:Free Radicals; D013858:Thiobarbiturates; C000981:5,6-dihydroxy-8-aminoquinoline; D006861:Hydrogen Peroxide; D007501:Iron; C029684:thiobarbituric acid; D011319:Primaquine; D010100:Oxygen