RESUMEN
Despite the Cox inhibitory anti-inflammatory and antipyretic effects of most widely used non-steroidal anti-inflammatory drugs (NSAIDs), such as Ibuprofen, their chronic use is associated with a plethora of patho-physiological insults. One such toxic effect on testicular tissues is not well studied and the underlying molecular mechanisms remain unexplored. Thus, the current study is designed to evaluate the antioxidant properties of essential trace element selenium (Se) to ameliorative Ibuprofen associated testicular toxic effects. Adult male Wistar rats were divided into 3 groups and fed on diets containing different concentrations of sodium selenite, viz. 0.01 mg/kg (Se- deficient), 0.2 mg/kg (Se-adequate), or 0.5 mg/kg (Se- supplemented) for 8 weeks. After diet feeding schedule, each group was divided into two subgroups i.e., with or without the treatment of Ibuprofen (120 mg/kg Bw). The protective effect of Se was evaluated by measuring testicular Se and selenoproteins status, spermatogenic markers, histopathology and testicular redox status. Ibuprofen diminished seminal volume, sperm count, sperm motility, which correlated well increased testicular reactive oxygen species. Se deficiency exacerbated these detrimental effects of ibuprofen by increasing oxidative stress. Alternatively, Se supplementation through antioxidant enzymes mediated protective effects. Se as essential antioxidant selenoproteins ameliorates Ibuprofen induced male reproductive toxicity.
Asunto(s)
Antiinflamatorios no Esteroideos/toxicidad , Ibuprofeno/toxicidad , Sustancias Protectoras/uso terapéutico , Selenito de Sodio/uso terapéutico , Testículo/efectos de los fármacos , Animales , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Masculino , Oxidación-Reducción , Oxidorreductasas/metabolismo , Sustancias Protectoras/farmacocinética , Sustancias Protectoras/farmacología , Ratas Wistar , Selenito de Sodio/sangre , Selenito de Sodio/farmacocinética , Selenito de Sodio/farmacología , Espermatozoides/efectos de los fármacos , Testículo/metabolismo , Testículo/patologíaRESUMEN
For the first time, bioavailability, pharmacokinetics, and biotransformation of selenium-enriched yeast (SeY) and sodium selenite (Na2SeO3) in rats were systemically compared by analyzing free selenomethionine (SeMet), total SeMet, and selenium (Se). After SeY and Na2SeO3 were orally administered to rats at a dose of 100 µg Se/kg, plasma free SeMet, total SeMet, and Se at various time points were determined by ultra-performance liquid chromatography-tandem mass spectrometry. Based on Se and total SeMet, the relative bioavailability values of SeY compared with Na2SeO3 were 144% and 272%, respectively. For the rats treated with SeY, 0.73-2.68% of total Se was biotransformed to free SeMet, 14.3-20.4% to SeMet-proteins and albumin-bound SeMet, and 75.9-82.3% to selenoproteins in plasma. SeY had higher bioavailability than Na2SeO3 based on Se and total SeMet levels. Plasma SeMet was the optimal biomarker of SeY status in vivo.
Asunto(s)
Saccharomyces cerevisiae/metabolismo , Selenio/sangre , Selenio/farmacocinética , Selenometionina/sangre , Selenito de Sodio/sangre , Selenito de Sodio/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Biomarcadores/sangre , Femenino , Masculino , Ratas , Ratas Sprague-Dawley , Saccharomyces cerevisiae/química , Selenio/administración & dosificación , Selenito de Sodio/administración & dosificaciónRESUMEN
Plants can play important roles in overcoming selenium (Se) deficiency and Se toxicity in various regions of the world. Selenite (SeIV), selenate (SeVI), as well as Se nanoparticles (SeNPs) naturally formed through reduction of SeIV, are the three main Se species in the environment. The bioaccumulation and transformation of these Se species in plants still need more understanding. The aims of this study are to investigate the phytotoxicity, accumulation, and transformation of SeIV, SeVI and SeNPs in garlic, a relatively Se accumulative plant. The spatial distribution of Se in the roots were imaged using synchrotron radiation micro-focused X-ray fluorescence (SR-µXRF). The chemical forms of Se in different plant tissues were analyzed using synchrotron radiation X-ray absorption spectroscopy (SR-XAS). The results demonstrate that 1) SeNPs which has the lowest phytotoxicity is stable in water, but prone to be converted to organic Se species, such as C-Se-C (MeSeCys) upon uptake by root. 2) SeIV is prone to concentrate in the root and incorporated into C-Se-C (MeSeCys) and C-Se-R (SeCys) bonding forms; 3) SeVI with the lowest transformation probability to organic Se species has the highest phytotoxicity to plant, and is much easier to translocate from root to leaf than SeNPs and SeIV. The present work provides insights into potential impact of SeNPs, selenite and selenate on aquatic-plant ecosystems, and is beneficial for systematically understanding the Se accumulation and transformation in food chain.
Asunto(s)
Ajo/metabolismo , Nanopartículas/metabolismo , Ácido Selénico/farmacocinética , Ácido Selenioso/farmacocinética , Selenio/farmacocinética , Selenito de Sodio/farmacocinética , Bioacumulación , Transporte Biológico , Biotransformación , Ajo/efectos de los fármacos , Hidroponía , Nanopartículas/toxicidad , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Ácido Selénico/toxicidad , Ácido Selenioso/toxicidad , Selenio/toxicidad , Selenito de Sodio/toxicidad , Espectroscopía de Absorción de Rayos XRESUMEN
The purpose of this research is to investigate the absorption, distribution, excretion, and pharmacokinetics of selenite in rats after intragastric administration, and thus illustrate the efficiency of selenium (Se) supplementation. After a single gavage of sodium selenite, a concentration of Se in plasma and tissues was determined by inductively coupled plasma mass spectrometry (ICP-MS) at different time points. Through fitting the data with the metabolic kinetic model, the corresponding kinetic parameters were determined for plasma and tissues, including kidney, liver, heart, muscle, and gonad. While the metabolic kinetics of sodium selenite in plasma, liver, and kidney of rats was well reflected by a two-compartment open model, that in heart and gonad was fitted to a one-compartment open model, and that in muscle was fitted to a one-compartment open model with a lag time. The results indicate that sodium selenite was absorbed by plasma and tissues quickly and was eliminated slowly after intragastric administration. Based on the results, we propose that multi-supplementation of Se with low dosage is superior to single supplementation with high dosage, in terms of avoiding selenosis.
Asunto(s)
Gónadas/metabolismo , Corazón , Riñón/metabolismo , Hígado/metabolismo , Músculos/metabolismo , Selenito de Sodio/farmacocinética , Administración Oral , Animales , Femenino , Gónadas/química , Riñón/química , Cinética , Hígado/química , Masculino , Músculos/química , Ratas , Ratas Wistar , Selenito de Sodio/administración & dosificación , Selenito de Sodio/sangre , Distribución TisularRESUMEN
Since the potato is a new staple food in China, the production of selenium (Se)-enriched potato may be an effective approach for Se supplementation in Se-deficient populations. Herein, we biofortified potato via the foliar application of sodium selenate and sodium selenite at three growth stages and investigated the resulting Se contents and speciation. Results showed that selenate was more efficient than selenite in improving total Se, and the highest tuber Se concentration was obtained at the tuber bulking stage. However, the accumulation of inorganic Se was higher in tubers treated with selenate (31.9% of total Se) compared with the selenite treatment (1.5%). The major Se species in tubers treated with both selenite and selenate was selenomethionine, which accounted for â¼80.0% and â¼50.0% of total Se, respectively. The findings suggest that the foliar application of selenite during the tuber bulking stage is appropriate for the production of Se-rich potatoes.
Asunto(s)
Tubérculos de la Planta/química , Ácido Selénico/farmacología , Selenio/farmacocinética , Selenito de Sodio/farmacología , Solanum tuberosum/efectos de los fármacos , China , Hojas de la Planta/efectos de los fármacos , Tubérculos de la Planta/efectos de los fármacos , Ácido Selénico/farmacocinética , Ácido Selenioso/farmacocinética , Selenio/análisis , Selenometionina/metabolismo , Selenito de Sodio/farmacocinética , Solanum tuberosum/metabolismo , Distribución TisularRESUMEN
Selenium (Se) is a trace element in the environment. Although it is a necessary trace element for human and animal health, excessive Se can also pollute the environment and show toxic effects on humans and animals. Since the safe dose range of Se is narrow, it is important to study the pharmacokinetics of Se in order to make better use of the biological effects of Se. In the present study, we investigated the pharmacokinetic process of sodium selenate in healthy piglet plasma after either intramuscular injection or oral administrations, and examined dynamic changes of antioxidant system in healthy piglets after Se supplementation. The results showed that the Se reached the peak concentration of (0.2451 ± 0.0123) µg mL-1 at (0.4237 ± 0.0185) h following intramuscular injection administration and (0.1781 ± 0.0142) µg mL-1 at (2.1517 ± 0.1806) h following oral administration in the plasma. The average AUC of sodium selenite following intramuscular injection and oral administrations was (31.7260 ± 1.3574) and (75.1460 ± 3.4127) mg L-1 h-1, respectively. Total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), and superoxide dismutase (SOD) generally show an upward trend and malondialdehyde (MDA) shows a downward trend, regardless of intramuscular injection or oral sodium selenite. An increased concentration of Se was observed in the serum of healthy piglets after intramuscular injection and oral sodium selenite. Our results indicated that the pharmacokinetic process of sodium selenate in healthy piglet blood conforms to the two-chamber open model. Its pharmacokinetic properties are rapid absorption and slow excretion. Antioxidant systems in healthy piglets vary with Se levels, but there is a significant lag period compared with the latter. Our current findings will provide a more complete understanding of clinical rational Se supplementation and avoid contamination of the environment by overdose.
Asunto(s)
Selenito de Sodio/farmacocinética , Administración Oral , Animales , Antioxidantes/metabolismo , Inyecciones Intramusculares , Malondialdehído/sangre , Estrés Oxidativo/efectos de los fármacos , Selenito de Sodio/administración & dosificación , Selenito de Sodio/farmacología , Superóxido Dismutasa/metabolismo , PorcinosRESUMEN
Selenium (Se) is an essential trace element for humans and animals. Appropriate amount of Se in the body can prevent a variety of diseases. However, Se deficiency leads to pathological changes such as skeletal muscle necrosis and pancreatic atrophy in livestock and poultry. Se preparations are widely used in the prevention and treatment of Se-deficient disease, but there is no unified standard of medication, and the safe dose range of Se is narrow. Therefore, it is of great significance to study the pharmacokinetics of low-Se ducklings and to formulate drug administration schemes. In the present study, eighty 1-day-old healthy ducklings were randomly selected, and fed with low-Se diet to 30 days of age (blood Se content ⦠0.03 µg/mL). After the low Se duckling models were duplicated, blood samples and tissues of livers, pancreases, and thigh muscles were collected at different time points to detect Se content following oral administration of 0.1% sodium selenite (Na2SeO3) at 0.8 mg/kg BW, and the pharmacokinetics parameters were automatically calculated by MCPKP program. The results showed that pharmacokinetics characteristics of Na2SeO3 in blood, livers, and pancreases of ducklings were consistent with the first-order absorption and two-compartment open models; in thigh muscles was consistent with the first-order absorption and one compartment with a lag time open model. The primary kinetic parameters of Na2SeO3 in blood: the half-life of absorption was 5.9026 h, the time of reaching maximum concentration was 23.03 h, and the half-life of elimination was 131.13 h. The absorption of Na2SeO3 in livers was the quickest, pancreases and thigh muscles were in order of becoming slower, and the elimination of Na2SeO3 in thigh muscles was the quickest, livers and pancreases were in order of becoming slower. The administration parameters of multi-dose were calculated according to the kinetic of single-dose: loading dose (D*) was 1.7046 mg/kg BW, maintenance dose (D0) was 0.8 mg/kg BW, and dosing interval (τ) was 120 h. The results of this study can supplement and improve the theoretical system of Se metabolic kinetics, and provide experimental basis for the prevention and treatment of Se deficiency disease by rational drug use.
Asunto(s)
Patos , Hígado/química , Músculos/química , Pancrelipasa/química , Selenio/sangre , Selenio/deficiencia , Selenito de Sodio/administración & dosificación , Selenito de Sodio/farmacocinética , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Selenito de Sodio/sangre , Distribución TisularRESUMEN
The particle size of selenium (Se) sources could affect Se absorption and utilization, and thus it is hypothesized that the Se bioavailability might be higher in ultrafine sodium selenite (USSe) than in sodium selenite (SSe) for broilers because of USSe's smaller particle size. An experiment was conducted to investigate the relative bioavailability of Se as USSe relative to SSe for broiler chicks fed a conventional corn-soybean meal diet. A total of 504 one-d-old Arbor Acres commercial male broilers were randomly allotted to 1 of 7 treatments with 6 replicates per treatment in a completely randomized design involving in a 2 (Se sources) × 3 (added Se levels) factorial arrangement of treatments plus a Se-unsupplemented control diet containing 0.05 mg Se/kg by analysis for 21 d. The 2 Se sources were USSe and SSe, and the 3 added Se levels were 0.15, 0.30, or 0.45 mg Se/kg. The Se concentrations, glutathione peroxidase (GSH-Px) activities, and mRNA relative abundances in plasma, liver, or pancreas of broilers on day 14 and 21 were determined. The results showed that Se concentrations, GSH-Px activities in plasma, liver, and pancreas, and mRNA relative abundances in the liver and pancreas of broilers on day 14 and 21 increased linearly (P < 0.05) as the added Se-level increased. Furthermore, a difference (P < 0.05) between USSe and SSe was detected for GSH-Px mRNA relative abundance in the pancreas of broilers on day 14. On the basis of the slope ratios from the multiple linear regression of the pancreatic GSH-Px mRNA relative abundance of broilers at 14 d of age on daily dietary analyzed Se intake, the Se bioavailability of USSe relative to SSe (100%) was 158% (P < 0.05). The results from this study indicated that the Se from USSe was more available to broilers than the Se from SSe in enhancing the pancreatic GSH-Px mRNA expression.
Asunto(s)
Pollos/fisiología , Selenio/análisis , Selenito de Sodio/farmacocinética , Alimentación Animal/análisis , Animales , Disponibilidad Biológica , Dieta/veterinaria , Glutatión Peroxidasa/genética , Hígado/metabolismo , Masculino , Páncreas/metabolismo , Distribución Aleatoria , Selenito de Sodio/sangre , Glycine max , Zea maysRESUMEN
Band gap tunable cadmium selenide (CdSe) quantum dots (QDs) were synthesized within earthworms that emit in the middle of the visible spectrum. We demonstrated that this luminescence emission is a combination of the earthworm's protein and QD luminescence, such that the contribution of QDs in the luminescence was negligible. Eisenia fetida earthworms were used for QD biosynthesis and were exposed to different concentrations of CdCl2 and Na2 SeO3 in standard soil for an adequate exposure time. The size of the CdSe QDs based on the effective mass model was in agreement with the size measured from the transmission electron microscopy analysis, with an average diameter of 7 nm. Ultraviolet-visible and photoluminescence analyses confirmed the synthesis of CdSe QDs with unique absorption and luminescence at 430 nm and 605 nm, respectively.
Asunto(s)
Compuestos de Cadmio/metabolismo , Oligoquetos/metabolismo , Puntos Cuánticos/metabolismo , Compuestos de Selenio/metabolismo , Animales , Cloruro de Cadmio/farmacocinética , Calibración , Inactivación Metabólica , Mediciones Luminiscentes , Microscopía Electrónica de Transmisión , Oligoquetos/efectos de los fármacos , Puntos Cuánticos/química , Selenito de Sodio/farmacocinética , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
A 6-week trial was conducted to compare the effect of selenium (Se) from hydroponically produced Se-enriched kale sprout (HPSeKS), sodium selenite (SS), and Se-enriched yeast (SeY) in laying hens. A total of 144 40-week-old hens were randomly divided into four groups, according to a completely randomized design. Each group consisted of four replicates with nine hens per replicate. The dietary treatments were T1 (basal diet) and T2, T3, and T4 (basal diets supplemented with 0.30 mg Se/kg from SS, SeY, and HPSeKS, respectively). Results showed that Se supplement did not affect (p > 0.05) productivity and egg quality. Hens fed Se from HPSeKS and SeY exhibited higher (p < 0.05) Se bioavailability than hens fed Se from SS. Whole egg Se concentration of hens fed Se from HPSeKS was similar (p > 0.05) to that of hens fed Se from SeY, but higher (p < 0.05) than that of hens fed Se from SS. However, the breast muscle and heart tissue Se concentrations of hens fed Se from SS, SeY, and HPSeKS were not different (p > 0.05). The results of this trial demonstrated that Se from HPSeKS and SeY was more efficient than Se from SS on Se bioavailability and whole egg Se concentration in laying hens.
Asunto(s)
Brassica/metabolismo , Huevos/análisis , Selenio/metabolismo , Selenito de Sodio/metabolismo , Levadura Seca/metabolismo , Animales , Disponibilidad Biológica , Pollos , Dieta , Suplementos Dietéticos , Femenino , Hidroponía , Distribución Aleatoria , Plantones/metabolismo , Selenio/administración & dosificación , Selenio/farmacocinética , Selenito de Sodio/administración & dosificación , Selenito de Sodio/farmacocinética , Levadura Seca/administración & dosificaciónRESUMEN
Foliar Se fertilizers were applied to investigate the effects of Se forms on Se accumulation and distribution in the wheat-maize rotation system and residual concentration of Se in subsequent crops. Sodium selenite, sodium selenate, selenomethionine, chemical nano-Se, humic acid + sodium selenite, and compound fertilizer + sodium selenite were applied once at the flowering stage of wheat (30 g ha-1) and at the bell stage of maize (60 g ha-1). Compared with the control treatment, foliar Se applications significant increased the grain Se concentration of wheat and maize by 0.02-0.31 and 0.07-1.09 mg kg-1, respectively. Wheat and maize grain Se recoveries were 3.0-10.4 and 4.1-18.5%, respectively. However, Se concentrations in the grain of subsequent wheat and maize significantly decreased by 77.9 and 91.2%, respectively. The change of Se concentration in soil was a dynamic process with Se depletion after harvest of maize.
Asunto(s)
Agricultura/métodos , Fertilizantes , Selenio/farmacocinética , Triticum/química , Zea mays/química , China , Hojas de la Planta/efectos de los fármacos , Estaciones del Año , Selenio/metabolismo , Selenometionina/metabolismo , Selenometionina/farmacocinética , Selenito de Sodio/metabolismo , Selenito de Sodio/farmacocinética , Suelo/química , Distribución Tisular , Triticum/efectos de los fármacos , Triticum/crecimiento & desarrollo , Zea mays/efectos de los fármacos , Zea mays/crecimiento & desarrolloRESUMEN
It is thought that zinc and selenium deï¬ciency may play a signiï¬cant role in the etiology of prostate cancer. Although joint zinc and selenium supplementation is frequently applied in the prevention of prostate diseases, the bioavailability of these elements in the prostate after co-administration is still unknown. The study examines the effect of subchronic supplementation of zinc gluconate and selenium compounds (sodium selenite or selenomethionine), administered together or separately, on their bioavailability in the prostate, as well as the induction of metallothionein-like proteins (MTs) bound to zinc in the prostate and liver. Zinc concentration in the dorso-lateral lobe of the prostate was signiï¬cantly elevated already after the ï¬rst month of supplementation of zinc alone. In the supplementation period, the MTs level increased together with zinc concentration. In contrast, the ventral lobe of the prostate did not demonstrate signiï¬cantly higher levels of zinc until after three months of supplementation, despite the MTs induction noted after one-month supplementation. Increased selenium levels in the dorsolateral lobe were observed throughout the administration and post-administration periods, regardless of the selenium compound used or whether zinc was co-administered. The results of our studies suggested for the ï¬rst time that these elements should not be administered jointly in supplementation.
Asunto(s)
Suplementos Dietéticos , Gluconatos/farmacocinética , Próstata/metabolismo , Selenometionina/farmacocinética , Selenito de Sodio/farmacocinética , Animales , Disponibilidad Biológica , Esquema de Medicación , Quimioterapia Combinada , Gluconatos/administración & dosificación , Masculino , Ratas , Ratas Wistar , Selenometionina/administración & dosificación , Selenito de Sodio/administración & dosificaciónRESUMEN
A human in vivo metabolism study was carried out to investigate the impact of the trimethylselenium ion (TMSe) status on metabolism and toxicokinetics of sodium selenite and selenized yeast. Nine healthy human volunteers were orally exposed to 200 µg selenium as sodium selenite and seven with selenized yeast (100 µg selenium). In each intervention group, three subjects belong to TMSe eliminators. Blood samples were withdrawn before and up to 6 h after administration. Urine samples were collected before and within 24 h after administration. Total selenium (Se) was quantified in blood plasma and urine and low molecular Se species in urine. Selenium concentration in plasma increased from 84.5 ± 13.2 µg Se/L before to 97.4 ± 13.2 µg Se/L 2-3 h after selenite supplementation and 89.5 ± 12.9 µg Se/L to 92.1 ± 13.9 µg Se/L after selenized yeast intake. The oral ingestion caused an additional Se elimination via urine of 16.9 ± 10.6 µg/24 h (TMSe elim.: 10.8 ± 6.9 µg/24 h; non-TMSe elim.: 20.0 ± 11.3 µg Se/24 h) after selenite exposure and 11.8 ± 4.1 µg/24 h (TMSe elim.: 10.8 ± 4.6 µg/24 h; non-TMSe elim.: 12.6 ± 4.2 µg Se/24 h) after selenized yeast exposure. Methyl-2-acetamido-2-deoxy-1-seleno-ß-D-galactopyranoside (SeSug1) was the main metabolite in all urine samples, whereas TMSe was another main metabolite in TMSe eliminators' urine. After selenite exposure, a small amount of the dose (0.5 ± 0.2 %) was oxidized to selenate and rapidly excreted via urine. With the exception of selenite exposure in TMSe eliminators, the comparison of total Se and the sum of quantified Se species revealed a high renal portion of unidentified species. The study indicated a different metabolism of inorganic and organic Se compounds in human, but also crucial differences of Se metabolism in TMSe eliminators and non-TMSe eliminators.
Asunto(s)
Suplementos Dietéticos , Riñón/metabolismo , Eliminación Renal , Compuestos de Selenio/metabolismo , Selenometionina/metabolismo , Selenito de Sodio/metabolismo , Levaduras/metabolismo , Administración Oral , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Biotransformación , Suplementos Dietéticos/efectos adversos , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Selenometionina/efectos adversos , Selenometionina/farmacocinética , Selenito de Sodio/administración & dosificación , Selenito de Sodio/efectos adversos , Selenito de Sodio/farmacocinética , Adulto JovenRESUMEN
BACKGROUND: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients' refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. MATERIALS AND METHODS: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. RESULTS AND CONCLUSION: MTD was defined as 10.2 mg/m(2), with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m(2) under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.
Asunto(s)
Antineoplásicos/farmacocinética , Antineoplásicos/toxicidad , Neoplasias/tratamiento farmacológico , Selenito de Sodio/farmacocinética , Selenito de Sodio/toxicidad , Administración Intravenosa , Adulto , Anciano , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Determinación de Punto Final , Fatiga , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Náusea , Selenito de Sodio/sangre , Resultado del TratamientoRESUMEN
The effects of administering the selenocompounds, sodium selenite, methylseleninic acid (MSA), and seleno-L-methionine (SeMet) on glucose tolerance were compared in the nicotinamide (NA) and streptozotocin (STZ)-induced diabetic mouse model. ICR mice were intraperitoneally treated twice with STZ (100 mg/kg) 15 min after an injection of NA (120 mg/kg) at a 1-d interval. Non-fasting blood glucose levels were then monitored weekly while orally administering the selenocompounds at 158 µg Se/kg body weight with free access to a selenium-deficient diet for 5 weeks. The mean body weights of NA/STZ-induced diabetic mice were partly restored by the administration of selenocompounds, while SeMet led to a higher selenium content and glutathione peroxidase 1 activity in the pancreas. Non-fasting and oral glucose tolerance-tested blood glucose levels, which were elevated by NA/STZ, were significantly suppressed by the administration of SeMet. These results suggest that SeMet may improve glucose tolerance in a NA/STZ-induced mild diabetic mouse model by increasing bioavailability in the pancreas.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes , Compuestos de Organoselenio , Selenometionina , Selenito de Sodio , Animales , Disponibilidad Biológica , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Prueba de Tolerancia a la Glucosa , Glutatión Peroxidasa/metabolismo , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hígado/metabolismo , Masculino , Ratones Endogámicos ICR , Niacinamida , Compuestos de Organoselenio/farmacocinética , Compuestos de Organoselenio/farmacología , Compuestos de Organoselenio/uso terapéutico , Páncreas/metabolismo , Selenometionina/farmacocinética , Selenometionina/farmacología , Selenometionina/uso terapéutico , Selenito de Sodio/farmacocinética , Selenito de Sodio/farmacología , Selenito de Sodio/uso terapéutico , Estreptozocina , Glutatión Peroxidasa GPX1RESUMEN
The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements' bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver.
Asunto(s)
Cloruros/farmacocinética , Hígado/química , Hígado/metabolismo , Nanopartículas del Metal/química , Selenio/química , Selenito de Sodio/farmacocinética , Compuestos de Zinc/farmacocinética , Zinc/metabolismo , Animales , Masculino , Oxidación-Reducción , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Distribución TisularRESUMEN
The aim of this study was to compare the efficacy of a new organic Se (2-hydroxy-4-methylselenobutanoic acid [HMSeBA]) source (SO) with sodium selenite (SS) and selenized yeast (SY) at various dietary levels for growth performance and tissue Se deposition in growing pigs. A total of 112 crossbred (Pietrain × [Large White × Landrace]) gilts were allotted at an average body weight of 26.73 kg to 7 dietary treatments with 8 replicate pens of 2 pigs per pen. Pigs were fed basal diets unsupplemented or supplemented either with SS, SY, or SO each at 0.1 or 0.3 mg Se/kg of diet for 32 d. Feed intake and BW were recorded during the experimental period. At the end of the experiment, blood, liver, and psoas major muscle of all gilts were collected for total Se and relative bioavailability determination. No differences were observed on final BW, ADG, ADFI, and G:F among dietary treatments. All Se-supplemented groups exhibited greater total Se contents in plasma (P < 0.01) and liver (P < 0.01) compared with unsupplemented control group. However, Se retention in psoas major muscle was improved only when organic Se source (SY or SO) was added to diets (P < 0.01). Regardless the Se level, the Se deposition in muscle was greater (P < 0.01) in pigs supplemented with SO than those supplemented with SY. Slope ratio assay confirmed the greater bioavailability of Se from organic compared with inorganic Se and also revealed that the relative bioavailability of Se from HMSeBA for plasma, liver, and muscle Se response was 170, 141, and 162%, respectively, for SY. This study shows a potential advantage of HMSeBA supplementation in the increase of Se contents in pig tissues, indicating that this new organic Se source could be an alternative source of Se in swine nutrition.
Asunto(s)
Butiratos/metabolismo , Compuestos de Selenio/metabolismo , Selenito de Sodio/metabolismo , Sus scrofa/metabolismo , Alimentación Animal/análisis , Animales , Disponibilidad Biológica , Butiratos/administración & dosificación , Butiratos/sangre , Butiratos/farmacocinética , Dieta/veterinaria , Suplementos Dietéticos/análisis , Femenino , Hígado/metabolismo , Espectrometría de Masas , Músculo Esquelético/metabolismo , Distribución Aleatoria , Compuestos de Selenio/administración & dosificación , Compuestos de Selenio/sangre , Compuestos de Selenio/farmacocinética , Selenito de Sodio/administración & dosificación , Selenito de Sodio/sangre , Selenito de Sodio/farmacocinética , Sus scrofa/crecimiento & desarrolloRESUMEN
Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome.
Asunto(s)
Antioxidantes/uso terapéutico , Cuidados Críticos/métodos , Ácido Selenioso/uso terapéutico , Selenito de Sodio/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , APACHE , Animales , Antioxidantes/administración & dosificación , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Enfermedad Crítica , Glutatión Peroxidasa/sangre , Humanos , Infusiones Parenterales , Metaanálisis como Asunto , Modelos Animales , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido Selenioso/administración & dosificación , Ácido Selenioso/farmacocinética , Selenio/sangre , Selenito de Sodio/administración & dosificación , Selenito de Sodio/farmacocinética , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Resultado del TratamientoRESUMEN
In order to identify the features of violations of free-radical processes in blood serum of 94 untreated cancer patients with different localization of the tumor (cancer of the stomach, colon, breast, ovarian, hemoblastoses) were determined selenium levels and indicators of oxidative stress (sum of metabolites of nitrogen--NOx, the level of superoxide dismutase--Cu/ZnSOD and malondiialdehyde-MDA, and the activity of catalase). In addition, 40 patients with malignant liver disease and clinical signs of liver failure in the early postoperative period was carried out a comparative evaluation of the efficacy of selenium-containing drug "Selenaze" (sodium selenite pentahydrate). It was found that selenium levels in cancer patients by 25-30% below the norm of 110-120 mg/l at a rate of 73.0 +/- 2.6 mg/l. Low levels of NOx was detected in patients with all tumor localizations (22.1 +/- 1.1 microM, with normal range 28.4 +/- 0.9 microM). The exceptions were patients with extensive malignant process in the liver, in which the NOx levels were significantly higher than normal (p < 0.001). The high level of NOx has a toxic effect on the hepatocyte, causing metabolic disorders and inflammatory-necrotic changes in the liver. Elevated levels of SOD and MDA in normal values of catalase activity was detected in all patients. The use of "Selenaze" in postoperative patients with tumors of the liver increased selenium levels by 10-12%, which was accompanied by a decrease in the content of SOD and NOx, and contributed to earlier recovery of detoxic and synthetic liver function. These findings point to an intensification of oxidative stress and metabolic disorders in the malignant process, which is the basis for metabolic correction.
Asunto(s)
Neoplasias/sangre , Óxidos de Nitrógeno/sangre , Estrés Oxidativo , Selenio/sangre , Superóxido Dismutasa/sangre , Femenino , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Selenito de Sodio/administración & dosificación , Selenito de Sodio/farmacocinética , Oligoelementos/administración & dosificación , Oligoelementos/farmacocinéticaRESUMEN
The effects of sodium selenite (SS) and selenium yeast (SY) alone and in combination (MS) on the selenium (Se) content, antioxidant enzyme activities (AEA), total antioxidant capacity (TAC), and oxidative stability of chicken breast meat were investigated. The results showed that the highest (p < 0.05) glutathione peroxidase (GSH-Px) activity was found in the SS-supplemented chicken breast meat; however, SY and MS treatments significantly increased (p < 0.05) the Se content and the activities of catalase (CAT), total superoxide dismutase (T-SOD), and TAC, but decreased (p < 0.05) the malondialdehyde (MDA) content at 42 days of age. Twelve days of storage at 4 °C decreased (p < 0.05) the activity of the GSH-Px, but CAT, T-SOD, and TAC remained stable. SY decreased the lipid oxidation more effectively in chicken breast meat. It was concluded that SY and MS are more effective than SS in increasing the AEA, TAC, and oxidative stability of chicken breast meat.