13-cis Retinoic acid ameliorates benzoyl peroxide-induced oxidative stress and hyperproliferative response in murine skin: a chemopreventive study

The present paper assesses the chemopreventive potential of retinoic acid on benzoyl peroxide (BPO)-induced cutaneous tumor promotion response and oxidative stress in murine skin. In this study, we have shown the activities of cutaneous antioxidant enzymes and phase II metabolizing enzymes and the glutathione content were decreased while epidermal ornithine decarboxylase (ODC) activity and DNA synthesis were induced in benzoyl peroxide treated animals. Topical application of retinoic acid resulted in significant inhibition of benzoyl peroxide-induced epidermal ornithine decarboxylase activity and DNA synthesis. Application of retinoic acid at three different doses prior to the application of benzoyl peroxide recovered the depleted level of glutathione, inhibited activities of antioxidant and phase II metabolizing enzymes, thus resulting in significant inhibition of oxidative stress in dose dependent manner. Enhanced susceptibility of cutaneous microsomal lipid peroxidation and xanthine oxidase activity were significantly reduced (P>0.05). The antimutagenic effect of retinoic acid was tested against benzoyl peroxide mediated mutagenicity in Salmonella typhimurium strain TA-98 and TA-100 using 3-methyl cholanthrene-induced murine skin (S9 fraction) as the metabolic activation system. Indeed, with the addition of various concentrations of retinoic acid there was significant reduction in the number of revertants per plate in concentration dependent manner. In summary, our data indicates that retinoic acid may exhibit cancer chemopreventive activity in skin tumorigenesis model.