RESUMO
BACKGROUND: The present study investigated whether sleep deprivation affects attention capture in young and older adults using event-related potentials (ERPs). METHODS: Eleven young adults (20-30 y) and nine older adults (60-70 y) were tested following both normal sleep (NS) and total sleep deprivation (TSD). ERPs were recorded during an auditory discrimination task consisting of standard and deviant stimuli. RESULTS: Deviant stimuli elicited the MMN, P3a, and RON ERPs. TSD attenuated the differences in reaction times between standards and deviants in young adults but not older adults. The P3a was attenuated in older adults compared to young adults. Older adults had a larger RON amplitude compared to young adults following NS, but not TSD. CONCLUSIONS: The reduced P3a and the absence of behavioral performance alteration in the older group suggests that older adults may utilize different neural processing strategies compared to younger adults to compensate for age-related declines in neural resources for attention capture. Sleep loss influenced age-related differences on the RON, suggesting that older adults may have reduced access to compensatory strategies following sleep loss.
Assuntos
Eletroencefalografia , Privação do Sono , Humanos , Idoso , Estimulação Acústica , Envelhecimento , Potenciais Evocados , Tempo de ReaçãoRESUMO
We aimed to investigate cortical and subcortical brain alterations in people with Parkinson's disease with polysomnography-confirmed rapid eye movement (REM) sleep behavior disorder (RBD). Thirty people with Parkinson's disease, including 15 people with RBD, were recruited and compared with 41 healthy controls. Surface-based cortical and subcortical analyses were performed on T1-weighted images to investigate thickness and shape abnormalities between groups, and voxel-based and deformation-based morphometry were performed to investigate local volume. Correlations were performed in patients to investigate the structural correlates of motor activity during REM sleep. People with RBD showed cortical thinning in the right perisylvian and inferior temporal cortices and shape contraction in the putamen compared with people without RBD. Compared with controls, people with RBD had extensive cortical thinning and volume loss, brainstem volume was reduced, and shape contraction was found in the basal ganglia and hippocampus. In comparison to controls, people without RBD showed more restricted thinning in the sensorimotor, parietal, and occipital cortices, reduced volume in the brainstem, temporal and more posterior areas, and shape contraction in the pallidum and hippocampus. In Parkinson's disease, higher tonic and phasic REM sleep motor activity was associated with contraction of the thalamic surface, extensive cortical thinning, and subtle volume reduction in the middle temporal gyrus. In Parkinson's disease, the presence of RBD is associated with extensive cortical and subcortical abnormalities, suggesting more severe neurodegeneration in people with RBD. This provides potential neuroanatomical correlates for the more severe clinical phenotype reported in people with Parkinson's disease with RBD.
Assuntos
Encéfalo/patologia , Doença de Parkinson/patologia , Transtorno do Comportamento do Sono REM/fisiopatologia , Sono REM/fisiologia , Idoso , Atrofia/patologia , Gânglios da Base/patologia , Tronco Encefálico/patologia , Feminino , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Doença de Parkinson/complicações , Polissonografia , Transtorno do Comportamento do Sono REM/complicações , Tálamo/patologiaRESUMO
Ample evidence suggests that consolidation of the memory trace associated with a newly acquired motor sequence is supported by thalamo-cortical spindle activity during subsequent sleep, as well as functional changes in a distributed cortico-striatal network. To date, however, no studies have investigated whether the structural white matter connections between these regions affect motor sequence memory consolidation in relation with sleep spindles. Here, we used diffusion weighted imaging (DWI) tractography to reconstruct the major fascicles of the cortico-striato-pallido-thalamo-cortical loop in both young and older participants who were trained on an explicit finger sequence learning task before and after a daytime nap. Thereby, this allowed us to examine whether post-learning sleep spindles measured using polysomnographic recordings interact with consolidation processes and this specific neural network. Our findings provide evidence corroborating the critical role of NREM2 thalamo-cortical sleep spindles in motor sequence memory consolidation, and show that the post-learning changes in these neurophysiological events relate specifically to white matter characteristics in thalamo-cortical fascicles. Moreover, we demonstrate that microstructure along this fascicle relates indirectly to offline gains in performance through an increase of spindle density over motor-related cortical areas. These results suggest that the integrity of thalamo-cortical projections, via their impact on sleep spindle generation, may represent one of the critical mechanisms modulating the expression of sleep-dependent offline gains following motor sequence learning in healthy adults.
Assuntos
Consolidação da Memória/fisiologia , Córtex Motor/fisiologia , Destreza Motora/fisiologia , Sono , Tálamo/fisiologia , Substância Branca/fisiologia , Adulto , Corpo Estriado/anatomia & histologia , Corpo Estriado/fisiologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Eletroencefalografia , Humanos , Pessoa de Meia-Idade , Atividade Motora , Córtex Motor/anatomia & histologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Polissonografia , Tálamo/anatomia & histologia , Substância Branca/anatomia & histologia , Adulto JovemRESUMO
Study Objectives: Sleep is a reliable indicator of cognitive health in older individuals. Sleep spindles (SS) are non-rapid eye movement (NREM) sleep oscillations implicated in sleep-dependent learning. Their generation imply a complex activation of the thalamo-cortico-thalamic loop. Since SS require neuronal synchrony, the integrity of the white matter (WM) underlying these connections is of major importance. During aging, both SS and WM undergo important changes. The goal of this study was to investigate whether WM integrity could predict the age-related reductions in SS characteristics. Methods: Thirty young and 31 older participants underwent a night of polysomnographic recording and a 3T magnetic resonance imaging acquisition including a diffusion sequence. SS were detected in NREM sleep and EEG spectral analysis was performed for the sigma frequency band. WM diffusion metrics were computed in a voxelwise design of analysis. Results: Compared to young participants, older individuals showed lower SS density, amplitude, and sigma power. Diffusion metrics were correlated with SS amplitude and sigma power in tracts connecting the thalamus to the frontal cortex for the young but not for the older group, suggesting a moderation effect. Moderation analyses showed that diffusion metrics explained between 14% and 39% of SS amplitude and sigma power variance in the young participants only. Conclusion: Our results indicate that WM underlying the thalamo-cortico-thalamic loop predicts SS characteristics in young individuals, but does not explain age-related changes in SS. Other neurophysiological factors could better explain the effect of age on SS characteristics.
Assuntos
Envelhecimento/fisiologia , Fases do Sono/fisiologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiologia , Adulto , Fatores Etários , Idoso , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Eletroencefalografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Tálamo/diagnóstico por imagem , Tálamo/fisiologia , Adulto JovemRESUMO
Sleep benefits motor memory consolidation. This mnemonic process is thought to be mediated by thalamo-cortical spindle activity during NREM-stage2 sleep episodes as well as changes in striatal and hippocampal activity. However, direct experimental evidence supporting the contribution of such sleep-dependent physiological mechanisms to motor memory consolidation in humans is lacking. In the present study, we combined EEG and fMRI sleep recordings following practice of a motor sequence learning (MSL) task to determine whether spindle oscillations support sleep-dependent motor memory consolidation by transiently synchronizing and coordinating specialized cortical and subcortical networks. To that end, we conducted EEG source reconstruction on spindle epochs in both cortical and subcortical regions using novel deep-source localization techniques. Coherence-based metrics were adopted to estimate functional connectivity between cortical and subcortical structures over specific frequency bands. Our findings not only confirm the critical and functional role of NREM-stage2 sleep spindles in motor skill consolidation, but provide first-time evidence that spindle oscillations [11-17â¯Hz] may be involved in sleep-dependent motor memory consolidation by locally reactivating and functionally binding specific task-relevant cortical and subcortical regions within networks including the hippocampus, putamen, thalamus and motor-related cortical regions.
Assuntos
Eletroencefalografia/métodos , Neuroimagem Funcional/métodos , Hipocampo/fisiologia , Imageamento por Ressonância Magnética/métodos , Consolidação da Memória/fisiologia , Atividade Motora/fisiologia , Rede Nervosa/fisiologia , Putamen/fisiologia , Fases do Sono/fisiologia , Tálamo/fisiologia , Adulto , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Putamen/diagnóstico por imagem , Aprendizagem Seriada/fisiologia , Tálamo/diagnóstico por imagem , Adulto JovemRESUMO
Light regulates multiple non-image-forming (or nonvisual) circadian, neuroendocrine, and neurobehavioral functions, via outputs from intrinsically photosensitive retinal ganglion cells (ipRGCs). Exposure to light directly enhances alertness and performance, so light is an important regulator of wakefulness and cognition. The roles of rods, cones, and ipRGCs in the impact of light on cognitive brain functions remain unclear, however. A small percentage of blind individuals retain non-image-forming photoreception and offer a unique opportunity to investigate light impacts in the absence of conscious vision, presumably through ipRGCs. Here, we show that three such patients were able to choose nonrandomly about the presence of light despite their complete lack of sight. Furthermore, 2 sec of blue light modified EEG activity when administered simultaneously to auditory stimulations. fMRI further showed that, during an auditory working memory task, less than a minute of blue light triggered the recruitment of supplemental prefrontal and thalamic brain regions involved in alertness and cognition regulation as well as key areas of the default mode network. These results, which have to be considered as a proof of concept, show that non-image-forming photoreception triggers some awareness for light and can have a more rapid impact on human cognition than previously understood, if brain processing is actively engaged. Furthermore, light stimulates higher cognitive brain activity, independently of vision, and engages supplemental brain areas to perform an ongoing cognitive process. To our knowledge, our results constitute the first indication that ipRGC signaling may rapidly affect fundamental cerebral organization, so that it could potentially participate to the regulation of numerous aspects of human brain function.
Assuntos
Cegueira/metabolismo , Cegueira/terapia , Encéfalo/metabolismo , Cognição/fisiologia , Estimulação Luminosa/métodos , Fototerapia/métodos , Idoso , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor/fisiologiaRESUMO
BACKGROUND: Vulnerability to the reduction in natural light associated with fall/winter is generally accepted as the main trigger of seasonal affective disorder (SAD), whereas light therapy is a treatment of choice of the disorder. However, the relationship between exposure to light and mood regulation remains unclear. As compared with green light, blue light was shown to acutely modulate emotion brain processing in healthy individuals. Here, we investigated the impact of light on emotion brain processing in patients with SAD and healthy control subjects and its relationship with retinal light sensitivity. METHODS: Fourteen symptomatic untreated patients with SAD (34.5 ± 8.2 years; 9 women) and 16 healthy control subjects (32.3 ± 7.7 years; 11 women) performed an auditory emotional task in functional magnetic resonance imaging during the fall/winter season, while being exposed to alternating blue and green monochromatic light. Scotopic and photopic retinal light sensitivities were then evaluated with electroretinography. RESULTS: Blue light enhanced responses to auditory emotional stimuli in the posterior hypothalamus in patients with SAD, whereas green light decreased these responses. These effects of blue and green light were not observed in healthy control subjects, despite similar retinal sensitivity in SAD and control subjects. CONCLUSIONS: These results point to the posterior hypothalamus as the neurobiological substrate involved in specific aspects of SAD, including a distinctive response to light and altered emotional responses.
Assuntos
Cor , Hipotálamo/fisiopatologia , Transtorno Afetivo Sazonal/patologia , Estimulação Acústica , Adolescente , Adulto , Eletrorretinografia , Emoções/fisiologia , Feminino , Humanos , Hipotálamo/irrigação sanguínea , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Tempo de Reação , Adulto JovemRESUMO
The aim of this study was to evaluate the effects of a 200-mg administration of caffeine on polysomnographic sleep variables and quantitative sleep electroencephalography (EEG) in 12 young (20-30 years) and 12 middle-aged (40-60 years) moderate caffeine consumers (one to three cups of coffee per day). All subjects were submitted to both a caffeine (200 mg) and placebo (lactose) condition in a double-blind cross-over design. The conditions were separated by 1 week. Compared with the placebo condition, the evening ingestion of caffeine lengthened sleep latency, reduced sleep efficiency, and decreased sleep duration and amount of stage 2 sleep in both age groups. Caffeine also reduced spectral power in delta frequencies in frontal, central and parietal brain areas, but not in prefrontal (PF) and occipital regions. Moreover, caffeine increased spectral power in beta frequencies in frontal and central brain areas in both age groups. A suppression of spectral power in the PF area in low delta frequencies (0.5-1.00 Hz) and a rise in spectral power in the parietal region in high alpha (10.00-12.00 Hz) and beta frequencies (17.00-21.00, 23.00-25.00, 27.00-29.00 Hz) occurred solely in middle-aged subjects. No such changes were noticeable in young subjects. Generally, caffeine produced similar effects in young and middle-aged subjects. Only a few frequency bins showed more effects of caffeine in middle-aged subjects compared with young subjects. Furthermore, sleep EEG results do not entirely support the hypothesis that caffeine fully mimics the effects of a reduction of homeostatic sleep propensity when following a normal sleep-wake cycle.
Assuntos
Envelhecimento/fisiologia , Cafeína/farmacologia , Cafeína/uso terapêutico , Ritmo Circadiano , Hábitos , Transtornos do Sono-Vigília/epidemiologia , Sono/efeitos dos fármacos , Adulto , Idoso , Bebidas , Cafeína/administração & dosagem , Café , Estudos Cross-Over , Método Duplo-Cego , Esquema de Medicação , Eletroencefalografia/efeitos dos fármacos , Feminino , Lobo Frontal/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Fases do Sono/efeitos dos fármacosRESUMO
BACKGROUND: In colitis, iron therapy may be given to treat anemia, but it may also be detrimental based on our previous studies using a rat model with colitis where iron supplementation increased disease activity and oxidative stress. This effect was partially reduced by an antioxidant. AIMS: The aim of this study was to further evaluate, in rats with dextran sulfate sodium (DSS)-induced colitis, the effect of iron on neutrophilic infiltration, cytokines and nuclear factor kappa-B (NF-kappaB)-associated inflammation and to determine whether the addition of vitamin E would be beneficial. METHODS: Colitis was induced with DSS at 50 g/l in drinking water for 7 days. DSS rats were randomized to the following: DSS, receiving a control, non-purified diet (iron, 270 mg and DL-alpha-tocopherol acetate, 49 mg/kg); DSS+iron (diet+iron, 3,000 mg/kg); DSS+vitamin E (diet+DL-alpha-tocopherol acetate, 2,000 mg/kg); or the DSS+iron+vitamin E. Colonic inflammation, myeloperoxidase activity (MPO), lipid peroxides (LPO), proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6] and NF-kappaB binding activity were measured. RESULTS: The DSS+iron group showed a significant increase in inflammatory scores, MPO, TNF-alpha, IL-1, LPO and NF-kappaB activity compared to DSS or DSS+vitamin E. The addition of vitamin E to iron (DSS+iron+vitamin E group) significantly reduced the inflammatory scores, TNF-alpha and IL-6. None of the other parameters were affected. CONCLUSION: Iron increases disease activity in colitis, and this is associated with oxidative stress, neutrophilic infiltration, increased cytokines and activation of NF-kappaB. This detrimental effect was partially reduced by vitamin E.
Assuntos
Colite/metabolismo , Ferro/farmacologia , NF-kappa B/metabolismo , Oligoelementos/farmacologia , Animais , Antioxidantes/farmacologia , Colite/induzido quimicamente , Colite/prevenção & controle , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Sulfato de Dextrana , Suplementos Nutricionais , Modelos Animais de Doenças , Indicadores e Reagentes , Peróxidos Lipídicos/metabolismo , Masculino , NF-kappa B/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Vitamina E/farmacologiaRESUMO
Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may underlie many herb-drug interactions. Serial serum concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with milk thistle or black cohosh modified P-gp activity in vivo. Sixteen healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg daily) or black cohosh (40 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxicaps, 0.4 mg) was administered orally before and at the end of each supplementation and control period. Serial digoxin serum concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the serum concentration time curves from 0 to 3 h (AUC(0-3)), AUC(0-24), Cmax, apparent oral clearance of digoxin (CL/F), and elimination half-life were used to assess the effects of milk thistle, black cohosh, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC(0-3), AUC(0-24), and Cmax, whereas clarithromycin increased these parameters significantly (p < 0.01). Significant changes in digoxin half-life and CL/F were also observed with clarithromycin. No statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either milk thistle or black cohosh, although digoxin AUC(0-3) and AUC(0-24) approached significance (p = 0.06) following milk thistle administration. When compared with rifampin and clarithromycin, supplementation with these specific formulations of milk thistle or black cohosh did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.
Assuntos
Cimicifuga , Digoxina/farmacocinética , Preparações de Plantas/farmacologia , Silybum marianum , Administração Oral , Adulto , Área Sob a Curva , Claritromicina/administração & dosagem , Claritromicina/farmacocinética , Suplementos Nutricionais , Digoxina/antagonistas & inibidores , Digoxina/sangue , Esquema de Medicação , Feminino , Genes MDR/genética , Meia-Vida , Haplótipos/genética , Interações Ervas-Drogas , Humanos , Masculino , Preparações de Plantas/administração & dosagem , Rifampina/administração & dosagem , Rifampina/farmacocinética , Rifampina/urinaRESUMO
OBJECTIVES: Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of Citrus aurantium , Echinacea purpurea , milk thistle (Silybum marianum), or saw palmetto (Serenoa repens) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. METHODS: Twelve healthy volunteers (6 women, 6 men) were randomly assigned to receive C aurantium , E purpurea , milk thistle, or saw palmetto for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported "active" phytochemicals was determined for each supplement. RESULTS: Comparisons of presupplementation and postsupplementation phenotypic ratios suggested that these particular supplements had no significant effect on CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Phytochemical profiles indicated that C aurantium was devoid of the CYP3A4 inhibitor 6',7'-dihydroxybergamottin. Quantities of fatty acids, flavonolignans, and cichoric acid were consistent with label claims for saw palmetto, milk thistle, and E purpurea , respectively. CONCLUSIONS: Botanical supplements containing C aurantium , milk thistle, or saw palmetto extracts appear to pose a minimal risk for CYP-mediated herb-drug interactions in humans. Although the effects of E purpurea on CYP activity were minor, further study into the interaction potential of this botanical is merited.
Assuntos
Citrus/química , Sistema Enzimático do Citocromo P-450/metabolismo , Echinacea/química , Extratos Vegetais/química , Silybum marianum/química , Adrenérgicos/farmacocinética , Adulto , Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacocinética , Cromatografia Líquida de Alta Pressão , Debrisoquina/farmacocinética , Suplementos Nutricionais , Interações Medicamentosas , Feminino , Moduladores GABAérgicos/farmacocinética , Humanos , Isoenzimas/metabolismo , Cinética , Masculino , Midazolam/farmacocinética , Fenótipo , Extratos Vegetais/administração & dosagem , Serenoa , SolubilidadeRESUMO
Folate supplementation may reduce the risk of colorectal dysplasia and cancer in subjects with chronic ulcerative colitis (UC). The interleukin (IL) 2- and beta(2)-microglobulin (beta(2)m)-deficient (IL-2(null) x beta(2)m(null)) mice spontaneously develop colon cancer in the setting of chronic UC. This study investigated the effects of dietary folate on the development of UC-associated colon cancer in the IL-2(null) x beta(2)m(null) mice. Weaning IL-2(null) x beta(2)m(null) mice were randomized to receive 0 (deficient; n = 40), 2 (basal requirement; control; n = 46), or 8 (supplemented; n = 36) mg folate/kg diet for 32 weeks. At necropsy, all macroscopic colonic tumors were identified and histologically classified as dysplasia or adenocarcinoma. The incidence of high-grade lesions (high-grade dysplasia/carcinoma in situ and invasive adenocarcinoma) in the folate-supplemented group was 46% lower than that in the control group (35.3% versus 65.1%, P = 0.009). The incidence of high-grade lesions in the folate-deficient group was also 49% lower than that in the control group (33.3% versus 65.1%, P = 0.007). The higher mortality rate in the folate-deficient group compared with the other two groups (25% versus 6.5% and 5.6%, P < 0.02) partially accounted for the low incidence of high-grade lesions in this group. These data indicate that dietary folate supplementation at 4x the basal dietary requirement significantly suppresses UC-associated colorectal carcinogenesis in the IL-2(null) x beta(2)m(null) mice. These data also suggest that folate deficiency may inhibit colorectal carcinogenesis in chronic UC. However, the high mortality observed in the folate-deficient group precludes a definitive conclusion concerning the effect of folate deficiency on UC-associated colorectal carcinogenesis in this model.
Assuntos
Colite Ulcerativa/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Ácido Fólico/farmacologia , Interleucina-2/genética , Microglobulina beta-2/genética , Animais , Transformação Celular Neoplásica , Colite Ulcerativa/etiologia , Colite Ulcerativa/veterinária , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/fisiopatologia , Dieta , Suplementos Nutricionais , Modelos Animais de Doenças , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/veterinária , Humanos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Inflammatory bowel disease is often associated with iron deficiency anemia and oral iron supplementation may be required. However, iron may increase oxidative stress through the Fenton reaction and thus exacerbate the disease. This study was designed to determine in rats with dextran sulfate sodium (DSS)-induced colitis whether oral iron supplementation increases intestinal inflammation and oxidative stress and whether the addition of an antioxidant, vitamin E, would reduce this detrimental effect. Four groups of rats that consumed 50 g/L DSS in drinking water were studied for 7 d and were fed: a control, nonpurified diet (iron, 270 mg, and dl-alpha-tocopherol acetate, 49 mg/kg); diet + iron (iron, 3000 mg/kg); diet + vitamin E (dl-alpha-tocopherol acetate, 2000 mg/kg) and the diet + both iron and vitamin E, each at the same concentrations as above. Body weight change, rectal bleeding, histological scores, plasma and colonic lipid peroxides (LPO), plasma 8-isoprostane, colonic glutathione peroxidase (GPx) and plasma vitamin E were measured. Iron supplementation increased disease activity as demonstrated by higher histological scores and heavier rectal bleeding. This was associated with an increase in colonic and plasma LPO and plasma 8-isoprostane as well as a decrease in colonic GPx. Vitamin E supplementation decreased colonic inflammation and rectal bleeding but did not affect oxidative stress, suggesting another mechanism for reducing inflammation. In conclusion, oral iron supplementation resulted in an increase in disease activity in this model of colitis. This detrimental effect on disease activity was reduced by vitamin E. Therefore, the addition of vitamin E to oral iron supplementation may be beneficial.