Kaempferol-induced nuclear DNA damage and lipid peroxidation.
The extent of DNA damage and lipid peroxidation induced by kaempferol, a polyphenolic flavonoid with a molecular structure similar to quercetin, was studied under aerobic conditions in isolated rat-liver nuclei. Kaempferol induced significant (P < 0.05) concentration-dependent nuclear DNA degradation concurrent with lipid peroxidation; these effects were enhanced by iron(III) or copper(II). Catalase, superoxide dismutase (SOD), mannitol, and sodium azide did not show any inhibitory effect on the kaempferol-induced nuclear DNA damage in the presence of iron(III) or copper(II). On the other hand, all stimulated the kaempferol-induced DNA damage in the presence of iron(III); in the presence of copper(II) only SOD and mannitol showed statistically significant stimulatory effects. The kaempferol induced lipid peroxidation was significantly stimulated by catalase and sodium azide in the presence of iron(III). These results demonstrate the pro-oxidant properties of polyphenolic flavonoids, which are generally considered as antioxidants and anticarcinogens, suggesting their possible dual role in mutagenesis and carcinogenesis.
Division of Toxicological Research, Food and Drug Administration, Laurel, MD 20708.
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Sahu
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Gray
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002413:Cations, Divalent; D002474:Cell-Free System; D003300:Copper / Q000008:administration & dosage; D004249:DNA Damage; D005290:Ferric Compounds; D005419:Flavonoids; D066298:In Vitro Techniques; D007501:Iron / Q000008:administration & dosage; D044949:Kaempferols; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019810:Sodium Azide; D013482:Superoxide Dismutase / Q000494:pharmacology
D000975:Antioxidants; D001386:Azides; D002413:Cations, Divalent; D005290:Ferric Compounds; D005419:Flavonoids; D044949:Kaempferols; D008054:Lipid Peroxides; D008353:Mannitol; C006552:kaempferol; D003300:Copper; D019810:Sodium Azide; D011794:Quercetin; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase