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Tumour Biol ; 41(4): 1010428319846803, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31018830


Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis. This study was performed to analyze the role of mesenchymal stem cells as an alternative for cellular signaling growth factors involved in the pathogenesis of leukemogenesis in rats. Treatment of rats with 7,12-dimethyl benz [a] anthracene induced leukemogenesis appeared as a significant decrease in hematological parameters with concomitant significant increase in bone marrow oxidative and inflammatory indices (transforming growth factor beta and interleukin-6) in comparison with normal groups. On the contrary, Western immunoblotting showed a significant increase in the signaling growth factors: PI3K, AKT, mTOR proteins and a significant decrease in PTEN in 7,12-dimethyl benz [a] anthracene-treated group. In addition, a significant increase in the transcript levels of B cell lymphoma-2 protein gene in the 7,12-dimethyl benz [a] anthracene group, while that of C-X-C motif chemokine receptor-4 and B cell lymphoma-2 protein associated x-protein were significantly downregulated compared to controls. Meanwhile, therapeutic mesenchymal stem cells treatment predict a significant improvement versus 7,12-dimethyl benz [a] anthracene group through the modulation of growth factors that confront bone marrow dysplasia. In the same direction treatment of 7,12-dimethyl benz [a] anthracene group with mesenchymal stem cells, it induced apoptosis and increased the homing efficacy to bone marrow. In conclusion, mesenchymal stem cells improve hematopoiesis and alleviate inflammation, and modulated PI3K/AKT signaling pathway contributed to experimental leukemogenesis.

Leucemia/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proteína Oncogênica v-akt/genética , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Apoptose/genética , Células da Medula Óssea/patologia , Diferenciação Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Humanos , Leucemia/induzido quimicamente , Leucemia/genética , Leucemia/patologia , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases/genética , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Fator de Crescimento Transformador beta/genética
Int J Radiat Biol ; 90(12): 1179-83, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24937371


PURPOSE: To evaluate the modulator role of fish oil (FO) on some biochemical changes in the brain of gamma-irradiated rats (RAD). MATERIAL AND METHODS: Male albino rats Sprague Dawley were divided into four groups (n = 10). (i) CONTROL: received vehicle via gavages during 28 days; (ii) FO: received fish oil (400 mg/kg/day) via gavages during 28 days; (iii) RAD: received vehicle for 7 days before whole body gamma-irradiation with 8 Gy given in four fractions each 7 days apart and continued during the irradiation period; and (iv) FO+ RAD: received FO for 7 days before exposure to the first dose of irradiation and FO treatment was continued during the irradiation period. Animals were sacrificed 24 hours post the last irradiation dose. RESULTS: A significant increase of malondialdehyde (MDA) and protein carbonyl (CO) content associated with a significant decrease of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content were recorded in the brain of irradiated rats. Oxidative stress was accompanied by a significant decrease of eicosapentaenoic (EPA) and docosahexaenoic (DHA) levels. Aspartic (Asp) and glutamic (Glu) acid levels were increased. Serotonin level showed a decrease associated with enhanced monoamine oxidase (MAO) activity and increased 5-hydroxyindolacetic acid (5-HIAA) level. FO treatment reduced the severity of radiation-induced oxidative stress, alteration of Asp and Glu levels and serotonin metabolism concomitant with increased EPA and DHA levels. CONCLUSION: FO attenuates the severity of radiation-induced biochemical disorders in the brain by counteracting the radiation-induced decrease of EPA and DHA. Further studies are needed concerning the long-term implications of our findings.

Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Animais , Ácido Aspártico/metabolismo , Encéfalo/efeitos da radiação , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Raios gama/efeitos adversos , Ácido Glutâmico/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo
Int J Radiat Biol ; 88(8): 613-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22671307


PURPOSE: The purpose of this study was to evaluate the efficacy of hesperidin (HES), a citrus flavonoid, against the severity of biochemical disorders in the cerebral hemispheres of irradiated rats. MATERIAL AND METHODS: Hesperidin (50 mg/kg body weight) was administered to male albino rats via gavages during 10 successive days before whole body exposure to gamma rays (5 Gy) and during 14 days after irradiation. The animals were sacrificed on the 14th day post-irradiation. RESULTS: The results demonstrated a significant increase of the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (CO), and advanced oxidation protein products (AOPP), associated to significant decreases of total superoxide dismutase (tSOD) and catalase (CAT) activities, and reduced thiols content in the cerebral hemispheres of irradiated rats indicating oxidative stress. A significant decrease of the serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents and a significant increase of the activity of monoamine oxidase (MAO) were recorded, also, indicating alterations in the metabolism of monoamines. Moreover, a significant decrease of the activities of glutamate dehydrogenase (GDH) and creatine phophokinase (CPK), and a significant increase of calcium ions (Ca (+2)) levels were recorded in the mitochondria. Hesperidin treatment has significantly attenuated oxidative stress, monoamines alterations and mitochondrial damage in the cerebral hemispheres of irradiated rats. CONCLUSION: It could be concluded that hesperidin might attenuate the severity of radiation-induced biochemical disorders in brain tissues.

Cérebro/efeitos dos fármacos , Cérebro/efeitos da radiação , Hesperidina/farmacologia , Protetores contra Radiação/farmacologia , Animais , Monoaminas Biogênicas/metabolismo , Cérebro/enzimologia , Cérebro/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Ratos
Phytother Res ; 23(3): 434-8, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19003940


Whole body exposure to ionizing radiation induces the formation of reactive oxygen species (ROS) in different tissues provoking oxidative damage, organ dysfunction and metabolic disturbances. The present study was designed to determine the possible protective effect of grape seed extract (GSE), rich in proanthocyanidins against gamma-radiation-induced oxidative stress in heart and pancreas tissues associated with serum metabolic disturbances. Irradiated rats were whole body exposed to 5 Gy gamma-radiation. GSE-treated irradiated rats received 100 mg GSE/kg/day, by gavage, for 14 days before irradiation. The animals were killed on days 1, 14 and 28 after irradiation. Significant decreases of SOD, CAT and GSH-Px activities associated with significant increases of TBARS levels were recorded in both tissues after irradiation. GSE administration pre-irradiation significantly attenuated the radiation-induced oxidative stress in heart tissues which was substantiated by a significant amelioration of serum LDH, CPK and AST activities. GSE treatment also attenuated the oxidative stress in pancreas tissues which was associated with a significant improvement in radiation-induced hyperglycemia and hyperinsulinemia. In conclusion, the present data demonstrate that GSE would protect the heart and pancreas tissues from oxidative damage induced by ionizing irradiation.

Raios gama/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Protetores contra Radiação/farmacologia , Animais , Antioxidantes/farmacologia , Análise Química do Sangue , Masculino , Miocárdio/metabolismo , Oxirredução , Estresse Oxidativo/efeitos da radiação , Pâncreas/metabolismo , Pâncreas/efeitos da radiação , Lesões Experimentais por Radiação/prevenção & controle , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitis