RESUMEN
We previously showed that barley sprout extract (BSE) prevents chronic alcohol intake-induced liver injury in mice. BSE notably inhibited glutathione (GSH) depletion and increased inflammatory responses, revealing its mechanism of preventing alcohol-induced liver injury. In the present study we investigated whether the antioxidant effect of BSE involves enhancing nuclear factor-erythroid 2 related factor 2 (Nrf2) activity and GSH synthesis to inhibit alcohol-induced oxidative liver injury. Mice fed alcohol for four weeks exhibited significantly increased oxidative stress, evidenced by increased malondialdehyde (MDA) level and 4-hydroxynonenal (4-HNE) immunostaining in the liver, whereas treatment with BSE (100 mg/kg) prevented these effects. Similarly, exposure to BSE (0.1-1 mg/mL) significantly reduced oxidative cell death induced by t-butyl hydroperoxide (t-BHP, 300 µM) and stabilized the mitochondrial membrane potential (∆ψ). BSE dose-dependently increased the activity of Nrf2, a potential transcriptional regulator of antioxidant genes, in HepG2 cells. Therefore, increased expression of its target genes, heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase catalytic subunit (GCLC) was observed. Since GCLC is involved in the rate-limiting step of GSH synthesis, BSE increased the GSH level and decreased both cysteine dioxygenase (CDO) expression and taurine level. Because cysteine is a substrate for both taurine and GSH synthesis, a decrease in CDO expression would further contribute to increased cysteine availability for GSH synthesis. In conclusion, BSE protected the liver cells from oxidative stress by activating Nrf2 and increasing GSH synthesis.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Glutatión/biosíntesis , Hordeum/química , Subunidad p45 del Factor de Transcripción NF-E2/metabolismo , Extractos Vegetales/farmacología , Animales , Proteína con Homeodominio Antennapedia/farmacología , Supervivencia Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Proteínas de Drosophila/farmacología , Etanol/toxicidad , Células Hep G2 , Humanos , Peroxidación de Lípido , Masculino , Ratones , Subunidad p45 del Factor de Transcripción NF-E2/genética , Extractos Vegetales/química , Especies Reactivas de OxígenoRESUMEN
The effect of commercially available green tea (GT) and black tea (BT) drinks on drug metabolizing enzymes (DME) and oxidative stress in rats was investigated. Male Wistar rats were fed a laboratory chow diet and GT or BT drink for 5 weeks. Control rats received de-ionized water instead of the tea drinks. Rats received the GT and BT drinks treatment for 5 weeks showed a significant increase in hepatic microsomal cytochrome P450 (CYP) 1A1 and CYP1A2, and a significant decrease in CYP2C, CYP2E1 and CYP3A enzyme activities. Results of immunoblot analyses of enzyme protein contents showed the same trend with enzyme activity. Significant increase in UDP-glucuronosyltransferase activity and reduced glutathione content in liver and lungs were observed in rats treated with both tea drinks. A lower lipid peroxide level in lungs was observed in rats treated with GT drink. Electrophoretic mobility shift assay revealed that both tea drinks decreased pregnane X receptor binding to DNA and increased nuclear factor-erythroid 2 p45-related factor 2 binding to DNA. These results suggest that feeding of both tea drinks to rats modulated DME activities and reduced oxidative stress in liver and lungs. GT drink is more effective on reducing oxidative stress than BT drink.
Asunto(s)
Camellia sinensis/química , Estrés Oxidativo , Té/química , Animales , Antioxidantes/farmacología , Cafeína/sangre , Colesterol/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2 , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Citocromos/genética , Citocromos/metabolismo , Glutatión/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Subunidad p45 del Factor de Transcripción NF-E2/genética , Subunidad p45 del Factor de Transcripción NF-E2/metabolismo , Receptor X de Pregnano , Ratas , Ratas Wistar , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Triglicéridos/metabolismoRESUMEN
Friend murine leukemia virus (FMuLv) is an acutely oncogenic retrovirus, and its infection leads to erythroblastosis and leukemia in mice. This infection model is used in the search for new antiviral agents. In the present study, the authors have evaluated the potential of an extract of Phyllanthus amarus against FMuLv-induced erythroleukemia in BALB/c mice. Injection of newborn mice with FMuLv resulted in leukemia and animals died due to splenomegaly. Oral administration of P.amarus was found to enhance the life span of leukemia-harboring animals and decrease the incidence of anemia. The authors also performed a series of hematological, biochemical, histopathological, and gene expression analyses to evaluate the effect of P.amarus administration on erythroleukemia initiation and progression. The data obtained indicate that P.amarus administration could significantly decrease the progression of erythroleukemia. Treatment with P.amarus induced the expression of p53 and p45NFE2 and decreased the expression of Bcl-2 in the spleen of infected mice. Histopathological evaluations of the spleen demonstrated that administration of P.amarus decreased the infiltration of leukemic cells into the sinusoidal space when compared with the vehicle treated group. P.amarus is known to inhibit chemically induced neoplasm in different rodent models.The current results indicate that P.amarus has the ability to suppress virally induced cancers as well.
Asunto(s)
Virus de la Leucemia Murina de Friend , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Leucemia Experimental/tratamiento farmacológico , Phyllanthus/química , Extractos Vegetales/uso terapéutico , Infecciones por Retroviridae/tratamiento farmacológico , Infecciones Tumorales por Virus/tratamiento farmacológico , Anemia/sangre , Anemia/tratamiento farmacológico , Animales , Recuento de Células Sanguíneas , Peso Corporal/efectos de los fármacos , Transformación Celular Viral/efectos de los fármacos , Progresión de la Enfermedad , Expresión Génica/genética , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Leucemia Eritroblástica Aguda/sangre , Leucemia Eritroblástica Aguda/patología , Leucemia Experimental/sangre , Leucemia Experimental/patología , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Subunidad p45 del Factor de Transcripción NF-E2/genética , Tamaño de los Órganos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Infecciones por Retroviridae/sangre , Infecciones por Retroviridae/patología , Infecciones por Retroviridae/virología , Bazo/efectos de los fármacos , Bazo/metabolismo , Bazo/patología , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/genética , Infecciones Tumorales por Virus/sangre , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/virología , Ácido Úrico/sangreRESUMEN
OBJECTIVE: To explore the mechanism of acupuncture for delaying aging. METHODS: Using the senescence accelerated mouse pattern SAMP10 and the normal aging mice SAMR1 as models and applying RT-PCR and digoxin (DIG)-labeled Northern blot technique to observe expressions of NF-E2, YB-1, LRG47 genes in the forebrain, cortex and hippocampus in a 8-month old SAMR1 control group, a 8-month old SAMP10 control group, a 8-month old SAMP10 acupuncture group and a 8-month old SAMP10 non-point stimulation group. RESULTS: In the SAMP10 control group, the expressions of NF-E2, YB-1 and LRG47 were down-regulated in the forebrain, cortex and hippocampus, and after acupuncture they were up-regulated and tended to normal. CONCLUSION: The brain aging of the SAMP10 mice is related with abnormal expressions of NF-E2, YB-1 and LRG47 genes; and acupuncture can regulate the expressions of NF-E2, YB-1 and LRG47 genes, strengthening the functions of erythrocyte series, increasing the proliferation of cells and enhancing the cellular immune function in anti-bacteria, hence delaying aging.
Asunto(s)
Terapia por Acupuntura , Envejecimiento/genética , Proteínas de Unión al GTP/genética , Expresión Génica , Subunidad p45 del Factor de Transcripción NF-E2/genética , Factores de Transcripción/genética , Envejecimiento/metabolismo , Animales , Femenino , Proteínas de Unión al GTP/metabolismo , Humanos , Masculino , Ratones , Ratones Transgénicos , Modelos Animales , Subunidad p45 del Factor de Transcripción NF-E2/metabolismo , Distribución Aleatoria , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVE: To explore the mechanism of acupuncture in delaying aging. METHODS: Using SAMP10 mice and normal control SAMR1 as model and applying RT-PCR and DIG probed Northern blot techniques to observe expression of NF-E2, YB-1, LRG47 genes in whole brain, cortex and hippocampus in the 8-month SAMR1 control group, 8-month SAMP10 control group, 8-month SAMP10 acupuncture group and 8-month SAMP10 non-point acupuncture group. RESULTS: In the SAMP10 control group, the expression of NF-E2, YB-1 and LRG47 were down-regulated in the whole brain, cortex and hippocampus, and after acupuncture they were up-regulated and tended to normal. CONCLUSION: Aging of the SAMP10 mouse brain is related with expression of NF-E2, YB-1 and LRG47 genes, and acupuncture can regulate the expression of NF-E2, YB-1 and LRG47 genes, improving the functions of erythrocyte series, increasing proliferation of cells and immune function of cells in anti-bacteria, hence anti-aging.