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The biggest challenge that resveratrol researchers are currently facing is its poor in vivo bioavailability. In mammals, resveratrol is metabolized by the intestine and liver, mainly into glucuronides and sulfonates. Resveratrol is very quickly metabolized, usually within 30–60 minutes after administration, although by changing some variables in how the drug is given, the peak plasma concentration can be delayed slightly. Because it is so quickly metabolized, it is difficult to use systemically as a drug treatment since it disappears from the plasma in such a short time. There are several ways that researchers are trying to combat this problem to make resveratrol treatment viable against skin cancers and diseases.
The problem of quick metabolism of resveratrol and the impact it has on treatment of melanoma is easily illustrated by two studies conducted by Niles et al published in 2003 and 2006. The same group demonstrated in vitro that resveratrol induced apoptosis in melanoma cells. The authors then studied the effects of resveratrol in A375 cells implanted tumors in athymic (nu/nu) mice. Several modes of resveratrol administration used in this study were via drinking water, oral feeding, and slow-release pellet implants in tumor proximity. Surprisingly, the authors did not find any effect of resveratrol against melanoma tumors in vivo. The authors then administered a 75 mg/kg bolus dose via gavage to non-tumor bearing athymic mice to determine the plasma concentration of resveratrol 5 minutes following treatment. It was found that resveratrol levels were significantly reduced in plasma and it was converted into metabolites such as resveratrol glucuronide and piceatannol. Similar problems were also reported in other cancers, including leukemia, lung and intestine. Also, gastrointestinal problems have been reported in some patients who have taken resveratrol as part of clinical trials.
One possible way to circumvent the problem of bioavailability for skin disorders is to apply resveratrol topically to the skin. This would allow resveratrol to come into direct contact with the area of interest, without the side effects associated with systemic metabolism.
Article Produced By
Department of Dermatology, University of Wisconsin, University of Wisconsin Carbone Cancer Center, Corresponding author: Nihal Ahmad, Medical Sciences Center,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060966/
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