RESUMO
The aim of this study was to evaluate the muscle profile of novel added-value beef cuts including the caudal tip of the M. infraspinatus (Bonanza Cut; TIP) and M. subscapularis (SUB) and two traditional sirloin steak cuts, M. gluteus medius (top sirloin; GLM) and M. rectus femoris (sirloin tip; REC). Samples were subjected to Warner-Braztler Shear Force (WBSF), sensory, cooking loss, and proximate analysis. The muscle TIP had superior values of subjective tenderness, juiciness, and slight off-flavor intensity when compared to all other muscles. The TIP and SUB were similar in WBSF. Cooking loss and moisture values of raw samples were lowest for TIP. Results suggest that TIP can provide enhanced eating experience for consumers and improved marketability for the meat industry.
Assuntos
Carne Vermelha/normas , Paladar , Animais , Bovinos , Culinária , Humanos , Músculo Esquelético , Carne Vermelha/classificaçãoRESUMO
The issue of adverse health effects of ambient air pollution has been extensively studied and reported worldwide over the past two decades. The urban area of Reno and Sparks in northern Nevada is one of two major urban centers in Nevada; the other is Las Vegas. The northern area, which has undergone a rapid population growth in the last decade, has special geographic characteristics and air pollution patterns. We conducted environmental epidemiological studies spanning the 1990s. This report summarizes the evidence and discusses the findings in relation to other studies. Ambient air pollution levels, even when below federal standards, have a marked potential to impact human health adversely. Air pollution was associated with (1) emergency room visits for asthma; (2) hospitalization for chronic obstructive pulmonary disease; (3) hospitalization for cardio-vascular disease; (4) elementary school absenteeism; and (5) low birth weight, preterm birth, and other adverse birth outcomes.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Asma/induzido quimicamente , Doenças Cardiovasculares/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Absenteísmo , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Animais , Asma/etiologia , Doenças Cardiovasculares/etiologia , Criança , Tratamento de Emergência , Estudos Epidemiológicos , Feminino , Hospitalização , Humanos , Recém-Nascido , Nevada , Gravidez , Resultado da Gravidez , Doença Pulmonar Obstrutiva Crônica/etiologia , Instituições AcadêmicasRESUMO
DNA damage is involved in carcinogenesis, aging and other degenerative diseases. The relationship between DNA strand breakage and beta-carotene (0.1-1.6 microM) was examined under different O(2) tensions and with other antioxidants: alpha-tocopherol (5-80 microM), ascorbic acid (10-160 microM) and mixtures of these antioxidants. Supercoiled plasmid DNA pBR322 was incubated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) to induce DNA strand breaks in the presence of antioxidants under 15, 150, and 760 torr of O(2) tension. Under 15 torr of O(2) tension, beta-carotene, alpha-tocopherol, ascorbic acid and mixtures of these antioxidants provided a dose-dependent protection against AAPH-induced DNA strand breaks. The best protection was achieved in the mixture of antioxidants. Under 150 torr of oxygen tension, the antioxidant effect of beta-carotene was diminished at > or = 0.8 microM. A prooxidant effect was found at 0.8 > or = microM beta-carotene, producing more single- and double-strand breaks. alpha-Tocopherol and ascorbic acid exhibited dose-dependent antioxidant effects at 150 torr of oxygen tension. Under 760 torr of O(2) tension, the prooxidant effect of 0.8 microM beta-carotene was significant, causing supercoiled DNA to completely breakdown to circular and linear forms. In addition, 760 torr of O(2) tension attenuated the antioxidant effects of alpha-tocopherol and ascorbic acid. Thus, beta-carotene causes concentration-dependent DNA breakdown at high O(2) tension. The protection of DNA from the prooxidant effects of beta-carotene afforded by alpha-tocopherol and/or ascorbic acid was limited at high O(2) tension.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Dano ao DNA/efeitos dos fármacos , Oxigênio/química , Vitamina E/farmacologia , beta Caroteno/farmacologia , DNA Super-Helicoidal/efeitos dos fármacos , OxirreduçãoRESUMO
Experiments were conducted to determine the antioxidant and prooxidant effects of beta-carotene, alpha-tocopherol and ascorbic acid on human lung cells at different oxygen (O(2)) tensions. Free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), was used to induce the cellular damage associated with lipid peroxidation, protein oxidation and DNA breaks. Under hypoxic conditions (0 torr O(2) tension) all compounds produced a concentration-dependent antioxidant effect. Mixtures of the three compounds exhibited greater protective affects than any individual compound. At 143 torr O(2) tension, all compounds exhibited concentration-dependent protective effects against AAPH-induced cellular lipid, protein and DNA damage. At 722 torr O(2) tension, cells exhibited a consistent increase in lipid peroxidation (isoprostane formation), protein oxidation (carbonyl formation) and DNA damage (p53 protein accumulation). beta-Carotene (1.5 microM) produced a prooxidant effect by promoting 12% isoprostane formation. Protein oxidation and DNA damage at 722 torr O(2) tension was not increased by beta-carotene; however, the antioxidant effect of beta-carotene was attenuated. The antioxidant effects of alpha-tocopherol, ascorbic acid, and mixtures of the three antioxidant compounds also were reduced by the high O(2) conditions. These results partially substantiate the hypothesis that the antioxidant and prooxidant effects of beta-carotene are dependent on O(2) tension and concentration of beta-carotene. Such findings may partially explain why selected populations, such as smokers, respond adversely when supplemented with beta-carotene.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Dano ao DNA , Pulmão/citologia , Espécies Reativas de Oxigênio , Vitamina E/farmacologia , beta Caroteno/farmacologia , Técnicas de Cultura de Células , Radicais Livres , Humanos , Peroxidação de Lipídeos , Pulmão/efeitos dos fármacos , Oxirredução , Estresse Oxidativo , Oxigênio/análise , Proteínas/metabolismo , Fumar/efeitos adversosRESUMO
beta-Carotene, alpha-tocopherol, and ascorbic acid were tested for their ability to inhibit, enhance, or react synergistically with O(2) (15, 150, 760 torr) and, 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) or 1,1'-azobis (cyclohexane-carbonitrile) (ACCN) in isolated rat liver microsomes. beta-Carotene did not protect against lipid peroxidation, i.e., malondialdehyde (MDA) formation, in microsomal samples incubated at 37 degrees C with aqueous soluble AAPH at all added beta-carotene concentrations and oxygen tensions. More MDA (16%, p < 0.001) was produced at 15 torr of O(2,) and 160 nmol/mg protein of beta-carotene compared to respective vehicle control. Individually, alpha-tocopherol and ascorbic acid exhibited antioxidant protection (ascorbic acid &z.Gt; alpha-tocopherol); however, a mixture of both compounds was no more protective than ascorbic acid alone. beta-Carotene demonstrated a concentration-dependent antioxidant affect at 15 torr O(2) (p < 0.01); but a prooxidant effect at higher O(2) at 150 and 760 torr (>57%, p < 0.001) by lipid-soluble ACCN. alpha-Tocopherol exhibited concentration-dependent inhibitory effects on microsomal MDA formation at all oxygen tensions, but was most effective under 150 torr. Ascorbic acid demonstrated a concentration-dependent antioxidant effect only at 150 torr. ACCN-induced lipid peroxidation was no greater for the combination of the three compounds than ascorbic acid added alone. Thus, antioxidant or prooxidant activities for beta-carotene, alpha-tocopherol, and ascorbic acid in microsomal suspensions are related to O(2) tension, solubility, antioxidant concentrations and are governed by complex interactions. Differences between AAPH- and ACCN-induced lipid peroxidation are related to differences in lipid solubility.
RESUMO
This study assessed the association between ambient air pollution and daily elementary school absenteeism in Washoe County, NV, between 1996 and 1998. All 57 elementary schools in Washoe County in northern Nevada were included in the data set. There was a total of 27,793 student enrollments during this study period. The daily average absence rate was 5.09% (+/-1.54%). Air pollutant values including PM(10), O(3), and CO were obtained from seven air monitoring stations. Weather variables were collected from five of seven stations and from the Western Regional Climate Center. The daily average concentrations of PM(10), CO, and O(3) were 32.44 microg/m(3), 2.73 ppm, and 37.45 ppb, respectively. Student absenteeism was regressed on the three air pollutants, weather variables, and other confounding factors, using autoregression analysis. After adjusting for the effects of weather variables, day of the week, month, and holiday indicators, and time trend, we found that CO and O(3) were statistically significant predictors of daily absenteeism in elementary schools. For every 1.0 ppm and 50 ppb increase in CO and O(3), the absence rate would increase 3.79% (95% CI 1.04-6.55%) and 13.01% (95% CI 3.41-22.61%), respectively. However, PM(10) values were negatively correlated with school absenteeism.
Assuntos
Absenteísmo , Poluição do Ar/efeitos adversos , Monóxido de Carbono/efeitos adversos , Criança , Humanos , Ozônio/efeitos adversos , Análise de Regressão , Instituições AcadêmicasRESUMO
The effect of beta-carotene on protein oxidation was examined under different oxygen (O(2)) tensions and with other antioxidants: alpha-tocopherol, ascorbic acid, and mixtures of antioxidants. Human serum albumin (HSA) was incubated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) to induce protein oxidation (carbonyl formation), under 15, 150, and 760 torr of O(2) tension. Antioxidant activity was related to O(2) tension, antioxidant concentrations and interaction between mixtures of antioxidants: (1) Under 15 torr of O(2), incubating HSA with AAPH, 1. 6 microM beta-carotene, 80 microM alpha-tocopherol, 160 microM ascorbic acid, and mixtures (0.1 microM beta-carotene, 5.0 microM alpha-tocopherol and 10 microM ascorbic acid) resulted in 24, 29, 39, and 44% reduction of carbonyl formation, respectively. (2) Under 150 torr of O(2) tension, the antioxidant effect of beta-carotene was decreased by 4% but increasing O(2) tension did not diminish the antioxidant effects of alpha-tocopherol, ascorbic acid, or antioxidant mixtures. (3). Under 760 torr of O(2) tension, adding 1. 6 microM beta-carotene resulted in 26% more carbonyl formation. (4) Under 760 torr of O(2) tension, the antioxidant effect of ascorbic acid was decreased 32% compared to what was observed at 150 torr of O(2) tension. Changes in O(2) tension had no effect on the antioxidant effect of alpha-tocopherol. The mixture of antioxidants inhibited carbonyl formation by 37% and was 7% less effective than that of 15 and 150 torr of O(2) tension. High concentration of beta-carotene produces more protein oxidation in the presence of high O(2) tension by a prooxidant mechanism. Mixtures of beta-carotene, alpha-tocopherol, and ascorbic acid provided better protective effects on protein oxidation than any single compound.
Assuntos
Antioxidantes/química , Ácido Ascórbico/química , Oxigênio/química , Albumina Sérica/química , Vitamina E/química , beta Caroteno/química , Amidinas/química , Ensaio de Imunoadsorção Enzimática , Humanos , Oxidantes/química , Oxirredução , Fenil-Hidrazinas/químicaRESUMO
This study assessed the association between ambient PM(10) pollution and daily hospital admissions for chronic obstructive pulmonary disease (COPD) in Reno-Sparks, Nevada, for the period 1990-1994. All three hospitals in the region were included. There was a total of 3115 admissions for COPD during this period. Daily ambient PM(10) values were available from one of seven air monitoring stations in this region. Weather variables including temperature and wind speed were also collected from this station. The daily average concentration of PM(10) was 36.55 microg/m(3). The generalized additive model (GAM) was used in the whole analysis. After adjusting for the effects of weather variables, day of week, seasons, and time trend, the results show that PM(10) is a statistically significant predictor for daily hospital admissions for COPD. The relative risk (RR) of hospital admissions for COPD for an interquartile increase (26.6 microg/m(3)) of the 24-h average level of PM(10) is 1.049 (95% CI 1.011-1.087).
Assuntos
Poluição do Ar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Pneumopatias Obstrutivas/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Hospitais Públicos , Humanos , Exposição por Inalação , Pneumopatias Obstrutivas/induzido quimicamente , Nevada/epidemiologia , Tamanho da Partícula , Admissão do Paciente/estatística & dados numéricos , Fatores de Risco , Estações do Ano , Saúde da População Urbana , Tempo (Meteorologia)RESUMO
Recent research suggests that some cases of cardiovascular mortality may be related to carbon monoxide (CO) air pollution. Clinically based studies indicate the adverse effects of CO on the cardiopulmonary system. However, little attention has been paid to the question of hospital admissions for cardiovascular illness caused by ambient CO levels. The present study assesses the association between hospital admissions for cardiovascular system illnesses and the ambient levels of CO in the Reno-Sparks, NV, area over a 6-yr period (1989-1994). Daily admissions to all three hospitals in the region and daily ambient concentrations of CO, monitored at five sites, were included. There were 32,705 total cardiovascular (CV) admissions, including 13,108 with the diagnosis of ischemic heart disease (IHD) during the study period. The average daily 1-h maximum level of CO was 3.09 ppm. After adjusting for day-of-the-week and seasonal effects and controlling for the effects of autocorrelation errors, both weighted least squares (WLS) and autoregressive integrated moving average (ARIMA) methods showed consistently positive relationships between the ambient CO level and different groups of cardiovascular admissions, although the male gender and age older than 60 groups tended to be most affected. Data suggest a positive correlation between ambient CO levels and hospital admissions for CV diseases.
Assuntos
Poluentes Atmosféricos/análise , Monóxido de Carbono/análise , Doenças Cardiovasculares/etiologia , Hospitalização , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine what effects enrichment of human low-density lipoprotein (LDL) with combinations of alpha-tocopherol and beta-carotene would exert on LDL oxidation and attempt to define the nature of the effects. METHODS: Human plasma was pooled and alpha-tocopherol and beta-carotene was added in a four-by-four design resulting in the enrichment of LDL with alpha-tocopherol and beta-carotene in varying concentrations. Enriched and control LDL was oxidized in Cu2+ mediated oxidation system and resistance of LDL to oxidation was determined by lag time, thiobarbituric acid reactive substances (TBARS) activity, and rate of oxidation. RESULTS: Increasing LDL alpha-tocopherol concentration had a linear relationship with lag time and a negative correlation with rate of oxidation. LDL beta-carotene concentration was linearly correlated with the rate of LDL oxidation and beta-carotene loss, and exponentially related to TBARS concentration. CONCLUSIONS: These results support earlier findings for the protective effect of a-tocopherol against LDL oxidation, and suggest that beta-carotene participates as a prooxidant in the oxidative degradation of LDL under these conditions. Since high levels of alpha-tocopherol did not mitigate the prooxidative effect of beta-carotene, these result indicate that increased LDL beta-carotene may cancel the protective qualities of alpha-tocopherol.
Assuntos
Antioxidantes/metabolismo , Lipoproteínas LDL/sangue , Vitamina E/sangue , beta Caroteno/sangue , Adolescente , Adulto , Cobre/farmacologia , Humanos , Cinética , Oxirredução , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Selenium is essential for both mammalian and avian species, although its metabolism in birds has been less thoroughly studied. Little information has been available on the kinetics of selenium in birds, especially as it relates to the teratogenicity seen in waterfowl consuming excessive amounts. This study describes the pharmacokinetics of small amounts of 75Se as selenious acid injected into female mallard ducks. Labeled selenium was injected into a wing vein of restrained animals and tissues taken at five different time points up to 24 h post-injection. Selenium levels as percent of injected dose were determined in liver, kidney, heart, lung, adrenals, thyroid, spleen, pancreas, ovaries, intestine, muscle and plasma. Estimates of kinetic parameters (uptake and elimination rates, time of maximum concentration and maximum concentration) were obtained with a non-linear kinetics computer program (PCNONLIN, SCI Software, Lexington, KY). Results showed four basic patterns of distribution, uptake and elimination. Visceral tissues exhibited a triphasic pattern with a rapid rise, a decline followed by a distinctive increase in levels between the last two time points. Brain uptake was continuous over the 24 h. Plasma rose rapidly and then declined to a constant level. The ovaries as a tissue of interest relating to the teratogenic effects of selenium showed the greatest relative increase at 24 h, suggesting kinetic mechanisms consistent with a pathway that might lead to accumulation of toxic levels and teratogenic effects during embryo development.
Assuntos
Selênio/farmacocinética , Animais , Patos , Feminino , Injeções Intravenosas , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Miocárdio/metabolismo , Pâncreas/metabolismo , Selênio/administração & dosagem , Baço/metabolismo , Teratogênicos/farmacocinética , Distribuição TecidualRESUMO
This symposium focused on the research which documents benefit and toxicity in beta-carotene supplementation. Reflecting on past and current studies, the panel of experts discussed: (1) the potential harm of a high intake of beta-carotene on selected populations, (2) biochemical antioxidant/prooxidant mechanisms of beta-carotene at the cellular level, (3) potential benefits of other carotenoids and antioxidants, and (4) future directions for research in beta-carotene and other antioxidants.
Assuntos
Antioxidantes/farmacologia , Carotenoides/farmacologia , Suplementos Nutricionais , beta Caroteno/farmacologia , Animais , Antioxidantes/toxicidade , Carotenoides/toxicidade , Linhagem Celular , Contraindicações , Métodos Epidemiológicos , Ácidos Graxos Insaturados , Corantes Fluorescentes , Previsões , Radicais Livres , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias/etiologia , Neoplasias/prevenção & controle , Estresse Oxidativo , Ensaios Clínicos Controlados Aleatórios como Assunto , Fumar , Relação Estrutura-Atividade , beta Caroteno/toxicidadeRESUMO
OBJECTIVE: This study was undertaken to investigate the relationship between beta-carotene intake and biochemical indices of antioxidant status in the blood of nine premenopausal women ages 18 to 42. METHODS: Nine healthy adult women were fed a low beta-carotene diet for 68 days. They were repleted with the same diet supplemented with beta-carotene (15 mg beta-carotene) for 28 days. During the last week of the study, they received an additional mixed carotenoid supplement. Indices of blood antioxidant status were measured on days 1, 29, 36, 43, 50, 64, 71, 92, and 99. RESULTS: We found significant increases of erythrocyte conjugated dienes between the 71st and 99th day of the study; increases of glutathione (GSH) peroxidase (GP) on day 43 and day 92 compared to a decrease on day 29; and decreases of GSH reductase throughout the treatment period. Erythrocyte catalase activities seemed to parallel GP activities. Erythrocyte oxidized glutathione (GSSG) levels were depressed both after beta-carotene depletion and repletion. beta-Carotene depletion/repletion had no effect on plasma vitamin E or GSH levels. Platelet GSH levels were depressed after beta-carotene depletion followed by elevated GSH levels after beta-carotene repletion. CONCLUSION: A diet low in beta-carotene and adequate in all other nutrients, including vitamin A, resulted in altered erythrocyte and platelet antioxidant indices; however, it had little impact on plasma GSH or vitamin E levels in young healthy women. Our results are consistent with the suggestion that carotenes may be important in the prevention of oxidative damage.
Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Dieta , Eritrócitos/metabolismo , beta Caroteno/administração & dosagem , Adolescente , Adulto , Antioxidantes/farmacologia , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Necessidades Nutricionais , beta Caroteno/sangue , beta Caroteno/farmacologiaRESUMO
A symposium entitled Impact of Nutrients on Cellular Lipid Peroxidation and Antioxidant Defense System was held at the 33rd Annual Meeting of the Society of Toxicology (SOT) at the Loews Anatole Hotel in Dallas, Texas. The symposium was sponsored by the Food Safety Specialty Section and focused on the role of particular nutrients in cellular lipid peroxidation and antioxidant defense system. Emphasis was placed on defining underlying mechanisms for damage and protection, as well as potential ramification in human health issues. The following are extractions of some of the highlights from each presentation.
Assuntos
Antioxidantes/metabolismo , Peroxidação de Lipídeos/fisiologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Radicais Livres , Glutationa/metabolismo , Humanos , Ferro/fisiologia , Enxofre/metabolismo , Vitamina E/uso terapêuticoRESUMO
Forty pregnant cynomolgus macaques were treated daily from gestational day 20 to 50 by nasogastric intubation of 0, 25, 150, or 300 micrograms selenium as L-selenomethionine/kg body weight. In each group, 7-8 pregnancies were terminated by hysterotomy at gestational day 100 +/- 2 and the fetuses were examined, while 2-3 pregnancies in each group were allowed to proceed to term. Selenium and soluble glutathione peroxidase were measured in: maternal, neonatal, and fetal plasma and erythrocytes; fetal kidney, liver, muscle, and placenta; and maternal breast milk. The area under the multidose maternal plasma selenium concentration:time curve, the maximum maternal plasma selenium concentration, and the maternal urinary selenium excretion rates were proportional to the L-selenomethionine dose. Selenium concentrations in all fetal and neonatal, tissues were also proportional to maternal L-selenomethionine dose. Glutathione peroxidase was affected only in maternal erythrocytes, fetal kidney, and neonatal plasma. The selenium concentration in fetal plasma was an average 33% of that in maternal plasma. Although selenium concentrations in macaque milk were doubled by the highest dose, intrauterine selenium accumulation accounted for the majority of the neonatal selenium body burden. Despite the elevated selenium concentrations in fetal tissues, neonatal blood, and milk, no deleterious effects on neonates were observed. These results suggest that primate fetuses are well protected against selenium toxicity arising from high maternal L-selenomethionine intakes.
Assuntos
Feto/metabolismo , Troca Materno-Fetal , Placenta/metabolismo , Selênio/farmacocinética , Selênio/toxicidade , Selenometionina/farmacocinética , Animais , Animais Recém-Nascidos , Eritrócitos/metabolismo , Feminino , Sangue Fetal , Idade Gestacional , Glutationa Peroxidase/metabolismo , Cinética , Macaca fascicularis , Leite/química , Gravidez , Selênio/sangue , Selenometionina/toxicidade , Distribuição TecidualRESUMO
Forty pregnant long-tailed macaques were treated daily for 30 d with 0, 25, 150, or 300 micrograms selenium as L-selenomethionine/kg body weight. Erythrocyte and plasma selenium and glutathione peroxidase specific activities, hair and fecal selenium, and urinary selenium excretion were increased by and were linearly related to L-selenomethionine dose. Hair selenium was most sensitive to L-selenomethionine dose, with an 84-fold increase in the 300 micrograms selenium/(kg-d) group relative to controls (r = 0.917). Daily urinary selenium excretion (80-fold, r = 0.958), plasma selenium (22-fold, r = 0.885), erythrocyte selenium (24-fold, r = 0.920), and fecal selenium (18-fold, r = 0.911) also responded strongly to L-selenomethionine. Erythrocyte and plasma glutathione peroxidase specific activities increased 154% and 69% over controls, respectively. Toxicity was associated with erythrocyte selenium > 2.3 micrograms/mL, plasma selenium > 2.8 micrograms/mL, and hair selenium > 27 micrograms/g. Plasma, erythrocyte, and hair selenium concentrations may be useful for monitoring and preventing the toxicity of L-selenomethionine administered to humans in cancer chemoprevention trials.
Assuntos
Selênio/análise , Selenometionina/administração & dosagem , Análise de Variância , Animais , Eritrócitos/química , Fezes/química , Feminino , Glutationa Peroxidase/sangue , Cabelo/química , Macaca fascicularis , Gravidez , Análise de Regressão , Selênio/sangue , Selênio/toxicidade , Selênio/urina , Selenometionina/toxicidadeRESUMO
20 adult female macaques (Macaca fascicularis) were given oral doses of L-selenomethionine (L-SeMet) equivalent to 0, 25, 150, 300 and 600 micrograms selenium (Se)/kg body weight, and plasma, erythrocyte, hair, faecal and urine Se concentrations were determined. The macaques were scheduled for 30 daily oral doses of L-SeMet, but systemic toxicity necessitated dose reduction in several animals; two macaques given 600 micrograms Se/kg body weight/day for 10-15 days died, and the concentration of Se in their tissues was determined and compared with Se concentrations in tissues collected from one untreated animal. Circulating and urinary Se concentrations in control macaques were within the normal human ranges. Plasma, erythrocyte, hair and urinary Se concentrations were generally dependent on the dose of L-SeMet administered. Plasma Se reflected more immediately exposure to L-SeMet, whereas erythrocyte Se concentrations increased and decreased more slowly. In some cases, erythrocyte Se was still increasing or showed a plateau after L-SeMet treatment was discontinued. Plasma Se concentrations of 6.7-7.3 ppm were observed in the two animals that died due to acute toxicity to L-SeMet. Neither plasma nor erythrocyte GPx activity was influenced by a single L-SeMet dose, but an increase in erythrocyte GPx activity occurred with continuous exposure. Total tissue Se increased 13-28-fold in macaques given 600 micrograms Se/kg body weight/day for 10-15 days, with the liver and kidneys containing the the highest Se concentrations.
Assuntos
Selênio/farmacocinética , Selenometionina/farmacocinética , Absorção , Administração Oral , Animais , Eritrócitos/enzimologia , Eritrócitos/metabolismo , Fezes/química , Feminino , Glutationa Peroxidase/sangue , Glutationa Peroxidase/urina , Cabelo/metabolismo , Macaca fascicularis , Selênio/toxicidade , Selenometionina/administração & dosagem , Selenometionina/toxicidade , Distribuição TecidualRESUMO
Vesicant-induced pathogenesis is initiated by rapid alkylation and cross-linking of DNA purine bases causing strand breaks leading subsequently to NAD depletion and cell death. We postulated that vesicants may also be associated with free radical-mediated oxidative stress distal to the site of exposure. To test this postulate in the lung, we injected 3 groups (n = 8) of 5-month-old, male, athymic, nude mice, weighing 30-35 g with a single subcutaneous (s.c.) injection (5 microliters/mouse) of butyl 2-chloroethyl sulfide (BCS), a monofunctional sulfur mustard analog. After 1, 24 and 48 h, we euthanized the treated mice along with 2 untreated control mice at each time point. We then pooled the control mice in one group (n = 6) and analyzed the lungs for biochemical indices of oxidative stress. We found that total lung weight was not altered after treatment, but wet/dry weight ratio decreased 18% (P less than 0.05) and hemoglobin content increased 50% and 36% at 1 and 24 h, respectively. The activity of glucose-6-phosphate dehydrogenase increased significantly, 40% at 1 and 24 h and 84% at 48 h and that of glutathione S-transferases was 60%, P less than 0.05 greater at all time points. Lipid peroxidation (estimated by the thiobarbituric acid test) and total protein content increased 3-fold and 2-fold, at 1 and 24 h, respectively. Total and oxidized glutathione contents were significantly elevated, 38% at 1 h and 64% at 24 h for the former and 45% at 24 h and 56% at 48 h for the latter. Because these changes are consistent with the cellular response to oxidative stress, we conclude that BCS injected subcutaneously, can cause changes in the lung possibly via a free radical-mediated mechanism.