Chemopreventive effect of Vitis vinifera extract on 12-O-tetradecanoyl-13-phorbol acetate-induced cutaneous oxidative stress and tumor promotion in murine skin

Vitis vinifera (grapes) is used as a fruit worldwide and known for its pharmacological properties. The present paper assesses the chemopreventive potential of Vitis vinifera against 12-O-tetradecanoyl-13-phorbol acetate (TPA)-mediated tumor promotion in 7,12-dimethyl-benz[a]anthracene (DMBA) initiated mice skin. Skin tumor initiation was achieved by a single topical application of DMBA (40 μg/animal/0.20 ml acetone) to mice. Two weeks after the initiation, promoting agent, TPA (5.0 μg/animal/0.2 ml acetone) was applied two times a week for 20 weeks. Pretreatment of Vitis vinifera 1 h prior to each application of TPA resulted in protection against cutaneous tumorigenesis in dose-dependent manner. This inhibition was evident when tumor data was considered as the percentage of mice with tumor and the number of tumors per mouse. We have shown that typical application of Vitis vinifera prior to that of TPA resulted in significant inhibition against TPA-caused induction of epidermal ODC activity (P < 0.001) and DNA synthesis. Application of Vitis vinifera at a dose level of 5.0 mg and 10.0 mg kg^-1 body weight in acetone prior to that of TPA treatment resulted in partial significant inhibition of oxidative stress in dose-dependent manner. The concomitant increase in the microsomal lipid peroxidation and xanthine oxidase activities were significantly reduced (P < 0.001). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes were recovered to the partial significant level. Hence, it can be suggested that Vitis vinifera can be used as a chemopreventive agent against oxidative stress and carcinogenesis.