Resveratrol is a dual purpose inhibitor of DNA damage (#35)
Resveratrol is a polyphenol present in a number of foods including grapes, mulberries, peanuts and also in red wine. Resveratrol has been shown to have anti-cancer and anti-aging effects. It has been established that resveratrol acts as an antioxidant, scavenging O2·− and ·OH free radicals and reducing lipid peroxidation. Resveratrol has also been identified as an inhibitor of a number of detoxifying enzymes which are responsible for bioactivation of particular toxins converting them to more harmful metabolites.
We have demonstrate the capacity of resveratrol to act as a dual purpose inhibitor by using an assay which measures two types of DNA damage, the FPG and hOGG1 modified comet assay. Early germ cells which express Cyp2e1 were isolated from male mice and treated with a toxin, acrylamide, which causes both oxidative and glycidamide adducts with DNA, hence leading to increased DNA damage. These glycidamide adducts occur because the enzyme Cyp2e1 converts the acrylamide to glycidamide, a more reactive compound. Resveratrol treatment (0.1µg/ml, 18hr) was shown to inhibit both types of adducts when the cells were treated with acrylamide (1µg/ml, 18hr), while having no effect on the damage caused by direct glycidamide treatment (1).
As acrylamide is a toxicant present in many food sources, particularly fried foods, humans are readily exposed to it in a chronic manner. Acrylamide is a carcinogen, neurotoxin and reproductive toxin in mice. In a chronic study mice were exposed to acrylamide (1µg/ml, 6 months) along with resveratrol (10mg/kg bw/ day, 6 months) revealing that resveratrol also has benefits in combatting DNA damage in male germ cells in vivo. Again, resveratrol reduced oxidative adducts and glycidamide adducts in the testis.
Hence, the health benefits of resveratrol also extend to preventing DNA damage caused by acrylamide, a toxin which exerts its reproductive toxicity particularly with exposure in males.
- Nixon, B.J., Katen, A.L., Stanger, S.J., Schjenken, J.E., Nixon, B., and Roman, S.D. (2014). Mouse Spermatocytes Express CYP2E1 and Respond to Acrylamide Exposure PLOS ONE 9, doi:10.1371.