Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism

Area of Science:

• Biochemistry
• Molecular Biology
• Oxidative Stress Research

Background:

• Oxidative stress, driven by reactive oxygen species (ROS), is implicated in DNA damage.
• Hydroxyl radicals (•OH) are potent oxidants contributing to cellular damage.
• Natural compounds are explored for their potential protective effects against oxidative damage.

Purpose of the Study:

• To evaluate the protective efficacy of fisetin against •OH-induced DNA damage.
• To elucidate the underlying antioxidant mechanisms of fisetin in vitro.

Main Methods:

• DNA protection assessed via malondialdehyde (MDA) levels.
• In vitro antioxidant assays including •OH, superoxide anion (•O2⁻), DPPH•, and ABTS•+ radical scavenging, and Cu(2+) reducing power.
• Determination of half-maximal inhibitory concentrations (IC50) for various assays.

Main Results:

• Fisetin demonstrated dose-dependent protection against •OH-induced DNA damage (IC50 = 1535.00±29.60 µM).
• Significant dose-dependent radical scavenging activity observed across •OH, •O2⁻, DPPH•, and ABTS•+ assays.
• Potent antioxidant capacity indicated by low IC50 values, particularly in ABTS•+ (2.43±0.14 µM) and Cu(2+) reducing power (1.49±0.16 µM) assays.

Conclusions:

• Fisetin effectively protects DNA from •OH-induced oxidative damage.
• The protective mechanism involves scavenging of ROS via hydrogen atom transfer (HAT) and/or single electron transfer (SET) pathways.
• The 3',4'-dihydroxyl moiety on fisetin's B ring is crucial for its antioxidant activity, facilitating oxidation to a stable ortho-benzoquinone.