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Interactions of flavonoids, trace metals, and oxygen: nuclear DNA damage and lipid peroxidation induced by myricetin
1Division of Toxicological Research, Food and Drug Administration, Laurel, MD 20708.
Abstract:
The extent of DNA damage and lipid peroxidation induced by myricetin, a polyphenolic flavonoid, were studied in isolated rat liver nuclei under aerobic conditions. Myricetin 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 inhibit myricetin-induced nuclear DNA damage in the presence of iron (III) or copper (II). However, all of these antioxidants stimulated myricetin-induced DNA damage in the presence of copper (II). Lipid peroxidation induced by myricetin was significantly inhibited only by SOD in the presence of copper (II), whereas it was enhanced 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 to be antioxidants and anticarcinogens, and suggest a dual role for these flavonoids in mutagenesis and carcinogenesis.
Insights
Myricetin, a flavonoid, can cause DNA damage and lipid peroxidation in liver cells, especially with iron or copper. This suggests a dual role for flavonoids in cancer development.
Area of Science:
- Biochemistry
- Toxicology
- Molecular Biology
Background:
- Polyphenolic flavonoids, like myricetin, are often considered beneficial antioxidants and anticarcinogens.
- However, their precise biological activities, particularly under oxidative stress, require further investigation.
Purpose of the Study:
- To investigate the potential pro-oxidant effects of myricetin on DNA and lipids in isolated rat liver nuclei.
- To determine the influence of transition metals (iron and copper) on myricetin-induced oxidative damage.
- To assess the impact of various antioxidants on myricetin's effects.
Main Methods:
- Isolated rat liver nuclei were treated with myricetin under aerobic conditions.
- The study assessed DNA degradation and lipid peroxidation.
- The effects of myricetin were examined in the presence and absence of iron (III), copper (II), and specific antioxidants (catalase, superoxide dismutase, mannitol, sodium azide).
Main Results:
- Myricetin induced significant, concentration-dependent DNA degradation and lipid peroxidation.
- These effects were potentiated by iron (III) and copper (II).
- Antioxidants showed complex and sometimes contradictory effects, with some stimulating DNA damage in the presence of copper (II) and only superoxide dismutase inhibiting lipid peroxidation.
Conclusions:
- Myricetin exhibits pro-oxidant properties, challenging its universal classification as solely an antioxidant.
- The interaction with transition metals like iron and copper is critical in mediating myricetin's oxidative effects.
- Flavonoids may possess a dual role in mutagenesis and carcinogenesis, acting as both protective and damaging agents depending on the cellular context.