RESUMEN
The present study evaluates the topical application of aloe vera (Av) leaf gel as a protective natural product against 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin lesions in Swiss albino mice and as an antioxidant for the systemic toxicity of DMBA in the presence and absence of chronic unpredictable stress (CUS). Animals were randomized into seven groups and sacrificed after 16 weeks of treatment. Av gel application along with DMBA + 12-O-tetradecanoylphorbol-13-acetate (TPA) was found to be effective in reducing tumor incidence, cumulative number of papillomas, tumor burden and tumor yield when compared to untreated groups. Furthermore, topical treatment with Av gel significantly increased the overall in vivo antioxidant status of mice. Conversely, lipid peroxidation levels were significantly decreased in skin and circulation. However, pre-exposure to CUS followed by DMBA + TPA + Av gel application reduced the chemopreventive efficacy of Av gel as evidenced by increased tumor incidence, tumor burden, tumor yield and MDA levels accompanied by decrease in the enzymatic and nonenzymatic antioxidants. These observations were further supported by the results of fluorescent studies and comet assay. The study demonstrates a reduction in the antioxidant and antitumor potential of Av gel in presence of CUS thereby, signifying the need of stress reduction during cancer chemopreventive trials.
Asunto(s)
Quimioprevención/métodos , Preparaciones de Plantas/farmacología , Neoplasias Cutáneas/prevención & control , Neoplasias Cutáneas/psicología , Estrés Fisiológico/fisiología , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Antioxidantes/farmacología , Carcinógenos/administración & dosificación , Masculino , Ratones , Distribución Aleatoria , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/patología , Acetato de Tetradecanoilforbol/administración & dosificaciónRESUMEN
BACKGROUND/AIM: Intense pulsed light (IPL) has been extensively applied in the field of dermatology and aesthetics; however, the long-term consequences of its use are poorly unknown, and to the best of our knowledge there is no study on the effect of IPL in neoplastic lesions. In order to better understand the molecular mechanisms underlying IPL application in the skin, we used an animal model of carcinogenesis obtained by chemical induction with 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). MATERIALS AND METHODS: Institute of Cancer Research (ICR) mice were administered DMBA and/or TPA and treated with IPL. Skin was evaluated by histopathology and 2DE-blot-MS/MS analysis. RESULTS: Our data evidenced an inflammatory response and a metabolic remodeling of skin towards a glycolytic phenotype after chronic exposure to IPL, which was accomplished by increased oxidative stress and susceptibility to apoptosis. These alterations induced by IPL were more notorious in the DMBA sensitized skin. Keratins and metabolic proteins seem to be the more susceptible to oxidative modifications that might result in loss of function, contributing for the histological changes observed in treated skin. CONCLUSION: Data highlight the deleterious impact of IPL on skin phenotype, which justifies the need for more experimental studies in order to increase our understanding of the IPL long-term safety.
Asunto(s)
Tratamiento de Luz Pulsada Intensa/efectos adversos , Neoplasias Cutáneas/etiología , Piel/efectos de la radiación , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Carcinógenos/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Glucólisis , Queratinas/metabolismo , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Distribución Aleatoria , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Acetato de Tetradecanoilforbol/administración & dosificaciónRESUMEN
OBJECTIVE: To optimize the conditions for the extraction of alkaloid palmatine from Tinospora cordifolia by using response surface methodology (RSM) and study its anticancerous property against 7,12-dimethylbenz(a)anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice. METHODS: The effect of three independent variables, namely, extraction temperature, time, and cycles was investigated by using central composite design. A single topical application of DMBA (100 µg/100 µL of acetone), followed 2 weeks later by repeated application of croton oil (1% in acetone three times a week) for 16 weeks, exhibited 100 percent tumor incidence (Group 2). RESULTS: The highest yield of alkaloid from Tinospora cordifolia could be achieved at 16 hours of extraction time under 40°C with 4 extraction cycles. Alkaloid administration significantly decreases tumor size, number, and the activity of serum enzyme when compared with the control (Group 2). In addition, depleted levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase and increased DNA damage were restored in palmatine treated groups. CONCLUSION: The data of the present study clearly indicate the anticancer potential of palmatine alkaloid in DMBA induced skin cancer model in mice.
Asunto(s)
Antineoplásicos/farmacología , Alcaloides de Berberina/farmacología , Extractos Vegetales/farmacología , Tinospora/química , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno/efectos adversos , Alanina Transaminasa/sangre , Animales , Antineoplásicos/administración & dosificación , Aspartato Aminotransferasas/sangre , Alcaloides de Berberina/administración & dosificación , Carcinógenos/administración & dosificación , Catalasa/metabolismo , Transformación Celular Neoplásica/inducido químicamente , Quimioprevención , Aceite de Crotón/administración & dosificación , Aceite de Crotón/efectos adversos , Daño del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Glutatión/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/prevención & control , Superóxido Dismutasa/metabolismoRESUMEN
A new and simple high-performance liquid chromatography method was developed and validated for the simultaneous determination of retinol, retinyl palmitate, ß-carotene, α-tocopherol and vitamin C in rat serum treated with Plantago Major L. and 7,12 dimethylbenz[a]anthracene. High-performance liquid chromatography analysis was performed utilizing an Inertsil ODS3 reversed phase column with methanol-tetrahydrofuran-water as mobile phase under gradient conditions, at 1.5 mL min(-1) flow rate and 25 °C. Diode-array detection was at 325, 450, 290 and 270 nm (retinol and retinyl palmitate), ß-carotene, α-tocopherol and vitamin C, respectively and runnig time 18 min. The high-performance liquid chromatography assay and extraction procedure proposed are simple, rapid, sensitive and accurate. The method was then applied for the determination of retinol, retinyl palmitate, ß-carotene, α-tocopherol and vitamin C in rat serum. Results of this study demonstrated that; at 60th day DMBA-treated group, there was a significant decrease in vitamin levels compared to the levels of control group. A significant increase was observed in vitamin levels of 7,12 dimethylbenz[α]anthracene+Plantago Major L.-treated group compared to the DMBA-treated group. Additionally, the results obtained in the study are found to be in agreement with data reported in the literature.
Asunto(s)
Ácido Ascórbico/sangre , Cromatografía Líquida de Alta Presión/métodos , Vitamina A/análogos & derivados , Vitamina A/sangre , alfa-Tocoferol/sangre , beta Caroteno/sangre , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno/metabolismo , Animales , Carcinógenos/administración & dosificación , Carcinógenos/metabolismo , Cromatografía Líquida de Alta Presión/economía , Diterpenos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/metabolismo , Plantago/química , Ratas , Ratas Wistar , Ésteres de Retinilo , Sensibilidad y EspecificidadRESUMEN
The status of lipid peroxidation, antioxidants, and detoxification enzymes were used as biochemical end points to assess the chemopreventive potential of geraniol, a monoterpene, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA in liquid paraffin, three times a week, for 14 weeks developed well-differentiated squamous cell carcinoma in the buccal pouch of golden Syrian hamsters. Although 100% tumor formation was noticed in hamsters treated with DMBA alone, intragastric administration of geraniol, at a dose of 250 mg/kg body weight (b.w.) to DMBA-treated hamster completely prevented the formation of oral tumors. Furthermore, geraniol significantly reduced lipid peroxidation by-products and improved the status of enzymatic and non-enzymatic antioxidants as well as modulated the status of phase I and phase II detoxification enzymes, favoring the excretion of carcinogenic metabolite, during DMBA-induced oral carcinogenesis. The present study concludes that the chemopreventive potential of geraniol relies on its anti-lipid peroxidative and antioxidant function as well as modulatory effects on phase I and II detoxification enzymes to excrete the carcinogenic metabolite, during DMBA-induced hamster buccal pouch carcinogenesis.
Asunto(s)
Carcinoma de Células Escamosas/prevención & control , Mucosa Bucal/patología , Neoplasias de la Boca/prevención & control , Terpenos/uso terapéutico , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Monoterpenos Acíclicos , Animales , Anticarcinógenos/administración & dosificación , Anticarcinógenos/uso terapéutico , Antioxidantes/metabolismo , Carcinoma de Células Escamosas/inducido químicamente , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Catalasa/metabolismo , Cricetinae , Glutatión Transferasa/metabolismo , Inactivación Metabólica , Peroxidación de Lípido , Masculino , Mesocricetus , Mucosa Bucal/metabolismo , Neoplasias de la Boca/inducido químicamente , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Superóxido Dismutasa/metabolismo , Terpenos/administración & dosificaciónRESUMEN
AIM: The present study was designed to evaluate effects of Plantago major extract on oxidative status in Wistar albino rats administrated 7,12-dimethylbenz(a)anthracene (DMBA). METHODS: Rats were divided into three equal groups of 6 animals each: Group 1 controls, group 2 treated with DMBA (100 mg/kg, single dose) and group 3 receiving the DMBA and the aqueous extract at 100 mg/kg/d for 60 days. RESULTS: Significant decrease in catalase (P < 0.05), carbonic anhydrase (p ≤ 0.01), reduced glutathione (GSH) (P < 0.01) and total protein (P < 0.01) values was observed in the DMBA group compared with the healthy controls and DMBA + Plantago major groups. CONCLUSION: The results suggest preventive effects of Plantago major on DMBA induced oxidative damage in Wistar albino rats that might be due to decreased free radical generation.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno/toxicidad , Antioxidantes/uso terapéutico , Carcinógenos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Plantago/química , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Anhidrasas Carbónicas/metabolismo , Carcinógenos/administración & dosificación , Catalasa/metabolismo , Glutatión/metabolismo , Ratas , Ratas WistarRESUMEN
Monascus -fermented products offer valuable therapeutic benefits and have been extensively used in East Asia. This study investigated the prevention of oral tumor formation and antioxidative ability of the ethanol extracts from red mold dioscorea (RMDE) on 7,12-dimethyl-1,2-benz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. The HBP was painted with DMBA three times per week for 14 weeks, and animals were painted with celecoxib, RMDE (50, 100, and 200 mg/kg of bw), and ethanol extracts from dioscorea (200 mg/kg of bw) on days alternate to the DMBA application. The results demonstrated that RMDE attenuated tumor formation by elevating the antioxidase activity and suppressing the overproduction of reactive oxygen species, nitric oxide, prostaglandin E(2), and pro-inflammatory cytokines in the HBP caused by DMBA induction. These results indicated that RMDE exerted anti-inflammatory and antioxidative activity to prevent oral cancer. Therefore, the metabolite from Monascus fermentation may serve as a possible functional edible substance for the prevention of oral cancer.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno/toxicidad , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Dioscorea/microbiología , Fermentación , Monascus/metabolismo , Neoplasias de la Boca/prevención & control , Boca/lesiones , Extractos Vegetales/farmacología , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Antiinflamatorios/metabolismo , Antioxidantes/metabolismo , Carcinógenos/administración & dosificación , Carcinógenos/toxicidad , Cricetinae , Dioscorea/metabolismo , Modelos Animales de Enfermedad , Humanos , Masculino , Mesocricetus , Boca/efectos de los fármacos , Boca/inmunología , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/inmunología , Extractos Vegetales/metabolismoRESUMEN
7,12-Dimethylbenz[a]anthracene (DMBA)-treated hairless mice exposed to UVB radiation were used to examine the effect of graded levels of vitamin B(6) [1, 7 or 35 mg pyridoxine (PN) HCl/kg] on skin tumorigenesis for 18 wk. Compared to the 1 mg PN HCl/kg diet, the 35 mg PN HCl/kg diet significantly elevated the incidence and multiplicity of skin tumors, while there was no difference in skin tumorigenesis between the 7 and 35 mg PN HCl/kg diets. Skin levels of oxidative stress markers (lipid peroxides and protein carbonyls) were unaffected by dietary treatment. Compared to the 1 mg PN HCl/kg diet, the 7 and 35 mg PN HCl/kg diets significantly elevated serum pyridoxal 5'-phosphate (PLP) without affecting the skin level of PLP. The results suggest that dietary supplemental vitamin B(6) exaggerates UVB-induced skin tumorigenesis in hairless mice without affecting oxidative stress in the skin.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Suplementos Dietéticos/efectos adversos , Neoplasias Cutáneas/metabolismo , Rayos Ultravioleta/efectos adversos , Deficiencia de Vitamina B 6/metabolismo , Vitamina B 6/farmacología , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Carcinógenos/administración & dosificación , Dieta/efectos adversos , Dieta/métodos , Relación Dosis-Respuesta a Droga , Femenino , Ratones , Ratones Pelados , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Fosfato de Piridoxal/sangre , Piridoxina/metabolismo , Piridoxina/farmacología , Piel/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Neoplasias Cutáneas/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Vitamina B 6/efectos adversos , Vitamina B 6/metabolismo , Deficiencia de Vitamina B 6/tratamiento farmacológico , Complejo Vitamínico B/efectos adversos , Complejo Vitamínico B/metabolismo , Complejo Vitamínico B/farmacologíaRESUMEN
We have previously reported that substantial amounts of tocotrienols were present in the skin of animals fed a diet containing a tocopherols and tocotrienols rich fraction (T-mix) extracted from palm oil, and further, that sesame lignans enhanced tocotrienol levels in the skin. The present studies were undertaken to determine whether dietary tocotrienols and those with sesamin could protect the skin from damage induced by UVB irradiation in hairless mice fed four diets: a vitamin E-free diet, a 50 mg/kg alpha-tocopherol diet, a 229 mg/kg T-mix (with 50 mg alpha-tocopherol) diet and a 229 mg/kg T-mix with 2 g/kg sesamin diet. In Experiment 1, mice were fed the diets for 6 wk, and half of the mice were exposed to 180 mJ/cm(2 )of UVB light once daily for 7 d. After the intensity of sunburn was scored, vitamin E and thiobarbituric acid reactive substances (TBARS) concentrations in the skin and liver were determined. In Experiment 2, hairless mice were initiated with a single application of 7, 12-dimethylbenz[a]anthracene (DMBA), then 1 wk later mice were fed the experimental diets and subjected to 180 mJ/cm(2) UVB irradiation twice weekly for 20 wk. Tumor incidences were counted once a week. Tocotrienols were detected in the skin of mice fed T-mix, but their concentrations were significantly lower than for alpha-tocopherol. Sesamin elevated tocotrienol contents in the skin. In spite of the high alpha-tocopherol contents, the effects of alpha-tocopherol on sunburn and incidence of tumor were slight. T-mix fed groups reduced the extent of sunburn and incidence of tumor, and further reduction of sunburn and incidence of tumor were observed in the T-mix with sesamin group. These results suggest that dietary tocotrienols protect the skin more strongly than alpha-tocopherol against damage induced by UVB and sesamin enhances tocotrienol effects.
Asunto(s)
Dioxoles/farmacología , Alimentos Formulados , Lignanos/farmacología , Papiloma/prevención & control , Neoplasias Cutáneas/prevención & control , Quemadura Solar/prevención & control , Tocotrienoles/farmacología , Rayos Ultravioleta/efectos adversos , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Antioxidantes/farmacología , Carcinógenos/administración & dosificación , Sinergismo Farmacológico , Femenino , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Pelados , Aceite de Palma , Papiloma/inducido químicamente , Aceites de Plantas/administración & dosificación , Piel/efectos de los fármacos , Piel/metabolismo , Neoplasias Cutáneas/inducido químicamente , Quemadura Solar/etiología , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Vitamina E/metabolismoRESUMEN
The use of transgenic rodents may overcome many limitations of traditional cancer studies. Regulatory perspectives continue to evolve as new models are developed and validated. The transgenic mouse, K6/ODC, develops epidermal tumors when exposed to genotoxic carcinogens. In this study, K6/ODC mice were evaluated for model fitness and health robustness in a 36-week study to determine oncogenic risk of residual DNA in vaccines from neoplastic cell substrates. K6/ODC and C57BL/6 mice were treated with T24-H-ras expression plasmid, carrier vector DNA, or saline topically or by subcutaneous injection. One group of K6/ODC mice received 7,12-dimethylbenz-[a]anthracene [DMBA] dermally. Only DMBA-treated mice developed papillomas by six weeks, increasing in incidence to 25 weeks. By week 11, many K6/ODC mice showed severe dehydration and dermal eczema. By week 32, (6/8) surviving K6/ODC mice showed loss of mobility and balance. Microscopic evaluation of tissues revealed dermal/sebaceous gland hyperplasia, follicular dystrophy, splenic atrophy, and amyloid deposition/neutrophilic infiltration within liver, heart, and spleen, in all K6/ODC mice. Pathology was not detected in C57BL/6 mice. Progressive adverse health, decreased survival, and failure to develop papillomas to the H-ras plasmid suggest that K6/ODC mice may be an inappropriate alternative model for detection of oncogenic DNA and pharmaceutical carcinogenicity testing.
Asunto(s)
Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Queratina-6/genética , Ornitina Descarboxilasa/genética , Neoplasias Cutáneas/inducido químicamente , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Pruebas de Carcinogenicidad/métodos , Carcinógenos/administración & dosificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Virus del Sarcoma Murino/genética , Neoplasias Cutáneas/patología , Bazo/efectos de los fármacos , Bazo/patología , TransfecciónRESUMEN
A study on the protective effect of alcoholic extract of the leaves of Ocimum sanctum on 3-methylcholanthrene (MCA), 7,12-dimethylbenzanthracene (DMBA) and aflatoxin B1 (AFB1) induced skin tumorigenesis in a mouse model has been investigated. The study involved pretreatment of mice with the leaf extract prior to either MCA application or tetradecanoyl phorbol acetate (TPA) treatment in a two-stage tumor protocol viz a viz, DMBA/TPA and AFB1/TPA. The results of the present study indicate that the pretreatment with alcoholic extract of the leaves of O. sanctum decreased the number of tumors in MCA, DMBA/TPA and AFB1/TPA treated mice. The skin tumor induced animals pretreated with alcoholic extract led to a decrease in the expression of cutaneous gamma-glutamyl transpeptidase (GGT) and glutathione-S-transferase-P (GST-P) protein. The histopathological examination of skin tumors treated with leaf extract showed increased infiltration of polymorphonuclear, mononuclear and lymphocytic cells, decreased ornithine decarboxylase activity with concomitant enhancement of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in the serum, implying the in vivo antiproliferative and immunomodulatory activity of leaf extract. The decrease in cutaneous phase I enzymes and elevation of phase II enzymes in response to topical application of leaf extract prior to MCA, AFB1, DMBA/TPA and AFB1/TPA treatment indicate the possibility of impairment in reactive metabolite(s) formation and thereby reducing skin carcinogenicity. Furthermore, pretreatment of leaf extract in the carcinogen induced animals resulted in elevation of glutathione levels and decrease in lipid peroxidation along with heat shock protein expression, indicating a scavenging or antioxidant potential of the extract during chemical carcinogenesis. Thus it can be concluded that leaf extract of O. sanctum provides protection against chemical carcinogenesis in one or more of the following mechanisms: (i) by acting as an antioxidant; (ii) by modulating phase I and II enzymes; (iii) by exhibiting antiproliferative activity.
Asunto(s)
Anticarcinógenos/farmacología , Carcinógenos/toxicidad , Ocimum/química , Extractos Vegetales/farmacología , Neoplasias Cutáneas/prevención & control , Piel/efectos de los fármacos , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Administración Tópica , Aflatoxina B1/administración & dosificación , Aflatoxina B1/análogos & derivados , Aflatoxina B1/toxicidad , Animales , Anticarcinógenos/aislamiento & purificación , Anticarcinógenos/uso terapéutico , Carcinógenos/administración & dosificación , Cocarcinogénesis , Femenino , Glutatión/metabolismo , Gutatión-S-Transferasa pi/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Interleucina-1beta/sangre , Interleucina-1beta/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Metilcolantreno/administración & dosificación , Metilcolantreno/toxicidad , Ratones , Ornitina Descarboxilasa/metabolismo , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Piel/metabolismo , Piel/patología , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/inducido químicamente , Acetato de Tetradecanoilforbol/administración & dosificación , Acetato de Tetradecanoilforbol/toxicidad , Factor de Necrosis Tumoral alfa/sangre , gamma-Glutamiltransferasa/metabolismoRESUMEN
Flaxseed contains several dietary components that have been linked to low breast cancer risk; i.e., n-3 polyunsaturated fatty acids (PUFAs), lignans and fiber, but it also contains detectable levels of cadmium, a heavy metal that activates the estrogen receptor (ER). Since estrogenic exposures early in life modify susceptibility to develop breast cancer, we wondered whether maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 25) might affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in the rat offspring. Our data indicated that both in utero and postnatal 5% and 10% flaxseed exposures shortened mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls. Further, when assessed in 8-week-old rats, in utero 10% flaxseed exposure increased lobular ER-alpha protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-beta protein levels in the terminal end buds (TEBs) lobules and ducts. Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the epithelial structures. In a separate group of immature rats that were fed 5% defatted flaxseed diet (flaxseed source different than in the diets fed to pregnant or lactating rats) for 7 days, cadmium exposure through the diet was six-fold higher than allowed for humans by World Health Organization, and cadmium significantly accumulated in the liver and kidneys of the rats. It remains to be determined whether the increased mammary cancer in rats exposed to flaxseed through a maternal diet in utero or lactation was caused by cadmium present in flaxseed, and whether the reduced mammary ER-beta content was causally linked to increased mammary cancer risk among the offspring.
Asunto(s)
Lino/química , Glándulas Mamarias Animales/efectos de los fármacos , Neoplasias Mamarias Animales/inducido químicamente , Preparaciones de Plantas/toxicidad , Efectos Tardíos de la Exposición Prenatal , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Adenocarcinoma/inducido químicamente , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Animales Recién Nacidos , Butileno Glicoles/metabolismo , Cadmio/administración & dosificación , Cadmio/toxicidad , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Lactancia , Lignanos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/patología , Neoplasias Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/patología , Preparaciones de Plantas/administración & dosificación , Preparaciones de Plantas/química , Embarazo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Estrógenos/metabolismoRESUMEN
The chemopreventive potential of rosemary (Rosmarinus officinalis) on 7,12-dimethlybenz(a)anthracene (DMBA) initiated and croton oil promoted mouse skin tumorigenesis was assessed. The modulatory effects of R. officinalis was monitored on the basis of the average latency period, tumor incidence, tumor burden, tumor yield, tumor weight and diameter as well as lipid peroxidation and glutathione level. The results indicate that R. officinalis leaves extract could prolong the latency period of tumor occurrence, decrease the tumor incidence, tumor burden and tumor yield. The average weight and diameter of tumors recorded were comparatively lower in the rosemary extract treated mouse groups. The level of lipid peroxidation was significantly reduced in blood serum and liver. Furthermore, depleted levels of glutathione were restored in RE-administered animal groups. Thus, at a dose rate of 500 mg/kg body wt/mouse, the oral administration of rosemary extract was found to be significantly protective against two-stage skin tumorigenesis.
Asunto(s)
Fitoterapia , Extractos Vegetales/farmacología , Rosmarinus/química , Neoplasias Cutáneas/tratamiento farmacológico , Carga Tumoral/efectos de los fármacos , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Aceite de Crotón/administración & dosificación , Glutatión/análisis , Glutatión/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/química , Hígado/efectos de los fármacos , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Hojas de la Planta/química , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/patologíaAsunto(s)
9,10-Dimetil-1,2-benzantraceno/toxicidad , Longevidad/efectos de los fármacos , Neoplasias Experimentales/mortalidad , Activador de Plasminógeno de Tipo Uroquinasa/genética , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Administración Oral , Animales , Aceite de Maíz/administración & dosificación , Aceite de Maíz/toxicidad , Femenino , Longevidad/genética , Ratones , Ratones Endogámicos , Ratones Transgénicos , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/patología , Tasa de Supervivencia , Factores de TiempoRESUMEN
In this work, the protective effect of Vitamin E plus selenium (Vit E+Se) and melatonin against 7,12-dimethylbenz(a)anthracene (7,12-DMBA)-induced changes in superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT) and carbonic anhydrase (CA) activities and malonedialdehyde (MDA) levels of mouse brain were compared. 12-month old mice were divided into four groups each including 10 animals. The first group served as control group. The second group was treated with 7,12-DMBA (20 mg/(kg day)). The third group was treated with 7,12-DMBA and Vitamin E (90 microg/(individual day)) and selenium (1.8 microg/(individual day)) simultaneously. The fourth group was treated with 7,12-DMBA and melatonin (4.2 mg/(kg day)) simultaneously. Treatment continued for 21 days after which the mice were sacrificed and brain homogenates were prepared. 7,12-DMBA treated group exhibited significantly decreased levels of brain SOD, GSHPx, CAT and CA activities and increased MDA levels as compared to control. Vitamin E+Se fully or partially restored enzyme inhibition except for SOD. Lipid peroxidation was also reduced in Vitamin E+Se treated group. Melatonin provided a better protection for SOD, GSHPx and CAT, and a plausible protection for CA activity. Protection against lipid peroxidation measured as MDA in melatonin treated group was appreciable although slightly lesser than the protection provided by Vitamin E+Se. The results imply that Vitamin E+Se and melatonin both provide chemoprevention against 7,12-DMBA-induced oxidative stress in mouse brain.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno/toxicidad , Antioxidantes/farmacología , Encéfalo/patología , Carcinógenos/toxicidad , Melatonina/farmacología , Selenio/farmacología , Vitamina E/farmacología , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Encéfalo/enzimología , Anhidrasas Carbónicas/farmacología , Carcinógenos/administración & dosificación , Catalasa/farmacología , Modelos Animales de Enfermedad , Femenino , Glutatión Peroxidasa/farmacología , Malondialdehído/análisis , Ratones , Estrés Oxidativo , Superóxido Dismutasa/farmacologíaRESUMEN
Selenium, an essential micronutrient, is associated with antioxidant functions, physiological defence mechanisms against different diseases including several types of cancers. Search for new selenium compounds with more chemopreventive activities and lesser toxicities are in progress. In the present study, the antioxidative roles of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated against 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil-induced two-stage mouse skin carcinogenesis model. The compound was administered orally in carcinogen-induced mice in two different non-toxic doses: 2 mg/kg body weight and 3 mg/kg body weight. Significant inhibition in the incidence of papilloma formation (58-80%) as well as in the cumulative number of papilloma per papilloma-bearing mouse were observed in the treated groups as compared with the carcinogen control group. The compound was also found to significantly upregulate different phase II detoxifying enzymes in liver cytosol such as glutathione-S-transferase (P<0.01), catalase (P<0.01) and superoxide dismutase (SOD) (P<0.01) when measured after 15 days and also after 12 weeks of first DMBA treatment. Lipid peroxidation measured as the thiobarbituric acid reactive substances in liver microsomes was significantly inhibited (P<0.05) in a dose-dependent manner by diphenylmethyl selenocyanate. Thus the compound exerts its chemopreventive activity by reducing papilloma formation during chemically induced carcinogenesis, which in turn, may be through modulating the level of lipid peroxidation and phase II detoxifying enzyme system at the doses evaluated.
Asunto(s)
Anticarcinógenos/farmacología , Compuestos de Organoselenio/farmacología , Papiloma/prevención & control , Neoplasias Cutáneas/prevención & control , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Administración Oral , Animales , Antioxidantes/farmacología , Carcinógenos/administración & dosificación , Carcinógenos/toxicidad , Aceite de Crotón/administración & dosificación , Aceite de Crotón/toxicidad , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/toxicidad , Femenino , Peroxidación de Lípido , Ratones , Papiloma/inducido químicamente , Neoplasias Cutáneas/inducido químicamenteRESUMEN
One of the most promising strategies for cancer prevention today is chemoprevention using readily available natural substances from vegetables, fruits, herbs and spices. Among the spices, saffron (Crocus sativus, L) a member of the large family Iridaceae, has drawn attention because apart from its use as a flavouring agent, pharmacological studies have demonstrated many health promoting properties including radical scavenging, anti- mutagenic and immuno-modulating effects. In the present study the effects of an aqueous infusion of saffron on two stage skin papillogenesis / carcinogenesis in mice initiated by 7-12 dimethyl benz[a] anthracin (DMBA) and promoted with croton oil were investigated. Significant reduction in papilloma formation was found with saffron application in the pre-initiation and post-initiation periods, and particular when the agent was given both pre- and post-initiation. The inhibition appeared to be at least partly due on modulatory effects of saffron on some phase II detoxifying enzymes like glutathione-S-transferase (GST) and glutahinoe peroxidase (GPx), as well as catalase (CAT) and superoxide dismutase (SOD).
Asunto(s)
Transformación Celular Neoplásica , Crocus/química , Papiloma/prevención & control , Preparaciones de Plantas/farmacología , Neoplasias Cutáneas/prevención & control , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Carcinógenos/administración & dosificación , Femenino , Ratones , Neoplasias Experimentales , Papiloma/veterinaria , Neoplasias Cutáneas/veterinariaRESUMEN
Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have evaluated the effect of S. anacardium nut milk extract on carbohydrate metabolizing enzymes and mitochondrial tricarboxylic acid cycle and respiratory enzymes in liver and kidney mitochondria of dimethyl benzanthracene-induced mammary carcinoma in Sprague-Dawley rats. Mammary carcinoma-bearing rats showed a significant rise in glycolytic enzymes (hexokinase, phosphoglucoisomerase and aldolase) and a simultaneous fall in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1,6-diphosphatase). The activities of mitochondrial enzymes isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase and cytochrome C oxidase were significantly lowered in mammary carcinoma-bearing rats when compared with control rats. S. anacardium nut extract administration to tumour-induced animals significantly lowered the glycolytic enzyme activities (hexokinase, phosphoglucoisomerase and aldolase) and there was a rise in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1,6-diphosphatase), which indicated an antitumour and anticancer effect. Comparison of normal control rats and rats administered S. anacardium only as drug control animals showed no significant variations in enzyme activities. S. anacardium nut extract administration to dimethyl benzanthracene-tumour-induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.
Asunto(s)
Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Ciclo del Ácido Cítrico/efectos de los fármacos , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Semecarpus , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Ensayos de Selección de Medicamentos Antitumorales , Transporte de Electrón/efectos de los fármacos , Enzimas/metabolismo , Femenino , Glucólisis/efectos de los fármacos , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/metabolismo , Mitocondrias/enzimología , Mitocondrias/metabolismo , Nueces/química , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , RatasRESUMEN
BACKGROUND: Our previous results have showed that oral glutamine (GLN) supplementation decreased carcinogenesis in 7,12-dimethylbenz[a]antracene (DMBA) breast cancer model. We also have found that GLN raises blood glutathione (GSH) levels in an implantable breast cancer model. The process of tumor growth was accompanied by depressed GSH production and increased levels of insulin-like growth factor-I (IGF-I) and transforming growth factor beta1 (TGF-beta 1). GSH is counter-regulatory to IGF-I. We therefore hypothesized that in DMBA model of breast cancer, the increased GSH levels seen with oral GLN would be associated with lowered levels of IGF-I &TGF-beta(1). METHODS: Time-dated pubertal Sprague-Dawley rats were gavaged at time 0 with 1 g/kg/day glutamine (GLN) (n = 18), isonitrogenous Freamine (FA) (n = 18), or water (H(2)O) (n = 18). Rats were further randomized on day 7 to 100 mg/kg DMBA or oil. After 14 days, the animals were sacrificed and blood GSH, IGF-1, TGF-beta 1, breast tissue, and gut mucosa GSH levels were measured. RESULTS: Oral GLN increased significantly blood, breast tissue, and gut mucosa levels of GSH in both DMBA and control groups in comparison with the control groups not treated with GLN. At the same time, the levels of blood IGF-I and TGF-beta 1 decreased significantly in both DMBA-treated and control groups. DMBA did not significantly affect any of these levels. CONCLUSIONS ;Oral GLN increased GSH levels and lowered IGF-I and TGF-beta 1 in a range that is considered clinically significant. However, the effect of GLN in maintaining normal gut GSH production in the presence of DMBA was much more significant. Inconsistent with our hypothesis, reduction in IGF and TGF-beta 1 levels did not correlate with DMBA's effect on gut GSH production.
Asunto(s)
Glutamina/administración & dosificación , Glutatión/análisis , Glutatión/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Factor de Crecimiento Transformador beta/sangre , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Animales , Arterias , Mama/química , Dieta , Femenino , Mucosa Intestinal/química , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1RESUMEN
OBJECTIVE: The chemopreventive activity and mechanism of dehydroepiandrosterone (DHEA) were studied. METHODS: Model of 7, 12-dimethylbenz (alpha) anthracene (DMBA) induced breast carcinoma in Sprague-Dawley rats, uitra-violet (UV)-induced DNA damage and Salmonella mutation assay were used. RESULTS: In DMBA-induced rat mammary tumor model, the rats were orally given daily DHEA for 2 weeks before DMBA and continued for 10 weeks after DMBA administration. The results showed significant inhibition of tumor development by DHEA. The incidence of mammary carcinoma also decreased significantly on daily dose of oral 25 mg/kg DHEA with the mean tumor volume per rat also remarkably reduced by 92%. Moreover, 25 mg/kg DHEA treatment could significantly increase the carcinoma latency for about 3.5 weeks as compared with the control. Using polymerase chain reaction (PCR) assay, in vitro 10(-9) mol/L DHEA showed significant inhibitory effect on UV-induced DNA damage by 90%. In Ames test, DHEA was found to decrease DMBA and benzo (alpha) pyrene-induced TA98 and TA100 His(+) revertants markedly and the number of Salmonella clones were significantly reduced by 53.2% and 73.0% on dose of 5 microgram DHEA/plate. It was also shown that in vitro 10(-7) mol/L DHEA could also effectively inhibit the G-6-PDH activity, which might play an important role in its chemoprophylaxis activities. CONCLUSION: The results strongly prove that DHEA is a potent cancer chemoprophylaxis agent, which exhibits inhibitory potential on mutation and chemical carcinogen in vivo and in vitro.