RESUMEN
We recently showed that Tarapod tannic acid (TA), a hydrolyzable tannin extracted from the pods of the Tara tree (Caesalpinia spinosa), was more effective than other tannins tested at inhibiting ultraviolet-B (UV-B)-stimulated hydrogen peroxide activity (an indirect measure of free radicals) in the skin of hairless mice. We also found that Tarapod TA inhibited UV-B-induced ornithine decarboxylase activity and UV-B-stimulated DNA synthesis, two biochemical markers linked to the skin tumor-promoting ability of this physical carcinogen. For this reason, we examined the effect of topical application, force feeding (gavage), and intraperitoneal injections of Tarapod TA on mouse skin chronically treated with UV-B light. Mice were initiated by a single topical application of 7,12-dimethylbenz[a]anthracene (50 nmol) and promoted by two weekly treatments with UV-B light (250 mJ/cm2) for 25 weeks. Topical application of Tarapod TA, 20 minutes before irradiation, resulted in a dose-dependent inhibition of tumor incidence (number of mice with tumors) and tumor yield (number of tumors/mouse), with 8 mg of TA inhibiting tumor yield by 70% at Week 25. Intraperitoneal injections of low doses (10 mg/kg mouse body wt), but not of high doses (25 mg/kg body wt), of TA afforded protection against UV-B-induced papillomas. However, the protection by intraperitoneal injection was lower than that observed by topical application: 10 mg/kg body wt of TA reduced tumor yield by 55%. The force feeding of 10 mg of Tarapod TA before irradiation failed to significantly inhibit the yield of tumors at the end of the experiment but delayed tumor appearance by six weeks. These results suggest that plant tannins administered topically or injected intraperitoneally reduce the tumor-promoting effects of UV-B radiation and thus could be useful photoprotectants.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias Inducidas por Radiación/prevención & control , Fitoterapia , Protectores contra Radiación/uso terapéutico , Neoplasias Cutáneas/prevención & control , Taninos/uso terapéutico , Rayos Ultravioleta , Administración Oral , Administración Tópica , Animales , Femenino , Inyecciones Intraperitoneales , Ratones , Ratones Pelados , Extractos Vegetales/uso terapéutico , Piel/patología , Piel/efectos de la radiación , Árboles/químicaRESUMEN
The anti-oxidant and anti-tumor promotion activities of several tannins extracted from plants were examined in mouse skin treated with ultraviolet B (UVB) radiation in vivo. Hydroperoxide production was found to be maximally stimulated at a UVB dose of 200 mj/cm2, beyond which no further stimulation occurred. Treatment of mouse skin with two UVB doses of 225 mj/cm2 each, applied at a 48 h interval gradually increases the hydroperoxide (HPx)-producing activity of the epidermis, which is maximally stimulated at 4 days and returns to control levels at 15 days. The magnitude of the HPx response is found to increase with repeated UVB treatments applied at a 48 h interval and reaches a maximum level following four treatments. Of the three tannins tested (Commercial TA, Tarapod TA, and Oak TA), Tarapod TA is found to be the most effective inhibitor of UVB-stimulated HPx activity. Pretreatment with Tarapod TA inhibits, in a dose-dependent manner, this HPx response to UVB radiation. Inhibition by Tarapod TA occurs when it is applied at distant times before (-12 h) or after (+24 h) UVB radiation. When applied 20 min before UVB radiation, twice a week for 25 weeks, 8 mg of Tarapod TA inhibits the incidence and yield of papillomas promoted by UVB light in initiated skin by 34 and 70% respectively. Furthermore, when 10 mg/kg of mouse body weight of Tarapod TA was injected intraperitoneally, for a period of 25 weeks, 20 min prior to UVB treatment, it inhibited the yield of papillomas by 44%, suggesting that plant tannins when administered by various means are useful photoprotectants.