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1.
Pharmacol Rep ; 70(6): 1073-1078, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30296743

RESUMO

BACKGROUND: Selenium (Se) is an essential micronutrient for animals and humans used in the prevention or treatment of cancer. Selol is a mixture of selenitetriglycerides, containing Se(IV). It does not exhibit mutagenic activity and is less toxic than inorganic sodium selenite containing Se(IV). The antioxidant properties of the Selol were demonstrated using the blood of healthy animals. The aim of the study was to evaluate Selol as a Se supplement by determining the effect of its administration on the Se level and the antioxidant status in the tissues. METHODS: We examined the effect of long-term (28-day) Selol 5% supplementation on the activity of antioxidant enzymes, including the main selenoenzymes in healthy mice organs, such as liver, brain, lungs, and testis. Enzyme activities of the tissue homogenates and the concentration of malondialdehyde (MDA) as a biomarker of oxidative stress were measured using spectrophotometric methods. The selenium concentrations in the tissues were determined by inductively coupled plasma mass spectrometer (ICP-MS) as well. RESULTS: A significant increase in glutathione peroxidase, thioredoxin reductase, and glutathione S-transferase activity as well as the MDA concentration was observed in most of the studied tissues during the Selol 5% supplementation. CONCLUSIONS: Long-term supplementation with the new Se(IV) compound - Selol 5% significantly affects the activity of antioxidant enzymes and the redox state in healthy mice organs. In the healthy population Selol 5% seems to be a promising new antioxidant compound.


Assuntos
Antioxidantes/metabolismo , Suplementos Nutricionais , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Selênio/metabolismo , Compostos de Selênio/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Composição de Medicamentos , Peroxidação de Lipídeos/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Compostos de Selênio/química , Testículo/efeitos dos fármacos , Testículo/metabolismo , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia
2.
Pharmacol Rep ; 67(1): 1-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25560568

RESUMO

BACKGROUND: Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the second leading cause of male cancer death. Data from epidemiological, eco-environmental, nutritional prevention and clinical trials suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in vitro in many cancer cell lines and can overcome the cell resistance to doxorubicin. Selol seems a promising compound for prostate cancer therapy. MATERIALS AND METHODS: The aim of the present study is the evaluation of Selol's influence on intracellular redox state (Eh) of prostatic tumors and the liver in androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of these mice. RESULTS AND CONCLUSIONS: The anticancer activity of Selol involves perturbation of the redox regulation in the androgen dependent hPCa (LNCaP) cells, but not in healthy cells. After Selol treatment, intracellular Eh has increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82 mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular environment. The difference decreases from 141 mV to 62 mV. The changes suggest that a tumor cell was probably directed toward apoptosis. This is exemplified in a significant decrease in cancer tumor mass by approx. 17% after the three weeks of Selol administration.


Assuntos
Antineoplásicos/farmacologia , Compostos de Selênio/farmacologia , Idoso , Animais , Antineoplásicos/farmacocinética , Cisteína/metabolismo , Cistina/metabolismo , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Selênio/análise , Selênio/farmacocinética , Compostos de Selênio/farmacocinética , Compostos de Sulfidrila/análise , Distribuição Tecidual , Triglicerídeos/farmacologia
3.
Pharmacol Rep ; 66(2): 301-10, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24911085

RESUMO

BACKGROUND: Selol is a novel organoselenium Se(IV) compound. It reveals lower potential of toxicity than sodium selenite and does not exhibit mutagenic activity. Its antioxidant and anticancer properties including overcoming cancer cell resistance to standard therapy of the drug were proven. This is the first publication describing the influence of Selol 5% on the activity of blood antioxidant status in vivo. MATERIALS AND METHODS: We investigated the influence of Selol 5% short-term (24h) and long-term (28 days) administration on the activity of antioxidant enzymes, including the main selenoenzymes, in healthy mice plasma and erythrocytes. Plasma oxygen radical absorbance capacity value (ORAC) and the concentration of malonyldialdehyde (MDA) in plasma as a biomarker of oxidative stress as well as the value of selenium (Se) concentration in erythrocytes were shown. RESULTS: A significant increase of the selenium dependent glutathione peroxidase (Se-GSHPx) activity in plasma and erythrocytes, plasma selenoprotein P concentration, ORAC values, and Se concentration were observed during long-term supplementation as well as after Selol 5% single-dose administration, with two distinct increases of activity a few hours after the beginning of the experiment and before its end. We found a decreased thioredoxin reductase (THRR) activity and an increased MDA level during Selol 5% long-term supplementation. Glutathione S-transferase activity (GST) remained unchanged. CONCLUSION: Selol 5% supplementation in vivo affects the selenoenzymes activities as well as the antioxidant status of plasma and erythrocytes. Selol 5% is an inhibitor of thioredoxin reductase activity, which can be important in anticancer therapy.


Assuntos
Antioxidantes/análise , Malondialdeído/sangue , Estresse Oxidativo , Compostos de Selênio/administração & dosagem , Animais , Suplementos Nutricionais , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Masculino , Camundongos , Selenoproteína P/sangue , Tiorredoxina Dissulfeto Redutase/metabolismo
4.
Food Chem Toxicol ; 45(2): 296-302, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17011101

RESUMO

Effects of short-term lyophilized beer (LB) consumption on normotensive (WKY) and hypertensive (SHR) rats are reported. It was found that LB contains high quantities of bioactive compounds and has a high antioxidant potential. The WKY and SHR rats were divided into four groups of 8, two experimental and two controls, which were named LBWKY and LBSHR and ControlWKY and ControlSHR, respectively. LB was given to the rats of the LBWKY and LBSHR groups intragastrically at a dose of 2.72 g/kg in a volume of 10 ml/kg for 10 days. The rats of the control groups received saline solution. The following indices were determined: body weight gain, heart rate, systolic blood pressure, using a tail cuff method and GABA accumulation in the hypothalamus and the pons-medulla as measured by GABA-T inhibition. It was found that the treatment of rats with LB had no effect on the blood pressure and heart rate values. In both rat strains, LB decreased GABA accumulation in the hypothalamus and the pons-medulla. A significant reduction of body weight gain was observed in both LB-treated groups when compared with the corresponding controls. In conclusion, LB contains high quantities of bioactive compounds and possesses a high antioxidant potential. Diet supplemented with LB causes significant reduction of the central GABAergic activity in WKY and SHR rats without any effect on cardiovascular function. In addition, in both animal strains there was an apparent inverse association between LB intake and body weight gains.


Assuntos
Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Cerveja , Hipertensão/tratamento farmacológico , Ácido gama-Aminobutírico/metabolismo , Animais , Cerveja/análise , Liofilização , Hipertensão/fisiopatologia , Hipotálamo/metabolismo , Masculino , Bulbo/metabolismo , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Aumento de Peso/efeitos dos fármacos
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