beta-carotene and Hypoxia

We previously demonstrated that acute exposure to hypoxia (3 h at 3000 m) increased oxidative stress markers. Thus, by using the 'living high-training low' (LHTL) method, we further hypothesized that intermittent hypoxia associated with endurance training alters the prooxidant/antioxidant balance.. Twelve elite athletes from the Athletic French Federation were subjected to 18-day endurance training. They were divided into two groups: one group (control group) trained at 1200 m and lived in hypoxia (2500-3000 m simulated altitude) and the second group trained and lived at 1200 m. The subjects performed an acute hypoxic test (10 min at 4800 m) before and immediately after the training. Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA), ferric-reducing antioxidant power (FRAP), lipid-soluble antioxidants normalized for triacylglycerols, and cholesterol and retinol were measured before and after the 4800 m tests.. After the training, MDA and AOPP concentrations were decreased in response to the 4800 m test only for the control group. Eighteen days of LHTL induced a significant decrease of all antioxidant markers (FRAP, P=0.01; alpha-tocopherol, P=0.04; beta-carotene, P=0.01 and lycopene, P=0.02) for the runners. This imbalance between antioxidant and prooxidant might result from insufficient intakes in vitamins A and E.. The LHTL model characterized by the association of aerobic exercises and intermittent resting hypoxia exposures decreased the antioxidant status whereas the normoxic endurance training induced preconditioning mechanisms in response to the 4800 m test.

Topics: alpha-Tocopherol; Altitude; Antioxidants; beta Carotene; Carotenoids; Exercise; Humans; Hypoxia; Lipid Metabolism; Lycopene; Male; Malondialdehyde; Oxidative Stress; Physical Endurance; Proteins; Reactive Oxygen Species; Running; Sports; Vitamin A; Vitamin E; Vitamins

Fucoxanthinol (FxOH), a metabolite of fucoxanthin, is known to inhibit tumorigenicity of human colorectal cancer stem cells (CCSCs) and their sphere formation. Hypoxic conditions and hypoxia-inducible factors (HIFs) are essential to maintain the stemness of CCSCs. We investigated effects of FxOH on sphere formation, intercellular energy metabolites in colonospheres formed from human colorectal HT-29 cells under hypoxic conditions.. FxOH at 50 μM suppressed HIF1α expression and activation of integrin, mitogen-activated protein kinase (MAPK), Wingless/integrated (WNT) and signal transducer and activator of transcription (STAT) signals. Moreover, expression of epithelial-mesenchymal transition- and apoptosis-related proteins in the colonospheres was lowered by FxOH. The level of glycine was reduced in hypoxic colonospheres under FxOH treatment.. FxOH attenuated the sphere formation of hypoxic colonospheres, in part, by suppressing HIF1α expression. Glycine could be a potential predictor for the activity of agents that inhibit sphere formation by hypoxic colonospheres.

Topics: beta Carotene; Biomarkers, Tumor; Cell Proliferation; Drug Monitoring; Epithelial-Mesenchymal Transition; Glycine; HT29 Cells; Humans; Hypoxia; Neoplastic Stem Cells; Spheroids, Cellular

Presently there is no neuroprotective pharmacological treatment of proven clinical safety and efficacy available. The purpose of this study was to investigate whether the beta-carboline, abecarnil (Abe), which has already passed clinical phase III trials in patients with anxiety disorders, is neuroprotective in in vitro models of cerebral ischemia or excitotoxicity. Abe (100 nM) protected cultured cortical neurons when applied 20 min before or 20 min after combined oxygen glucose deprivation (OGD). Furthermore, cultured cortical neurons were protected from NMDA excitotoxicity when Abe (100 nM) was administered 20 min before or concurrent with 100 microM NMDA. In contrast, in adult rat organotypic retinal cultures, Abe failed to protect retinal ganglion cells (RGCs) against glutamate (Glu) excitotoxicity. Thus, although our data demonstrate that Abe is a potential neuroprotectant in cultured neurons, the lack of effect in an organotypical model of Glu toxicity indicates that further study is required before Abe might be considered for human neuroprotection trials.

Topics: Analysis of Variance; Animals; beta Carotene; Carbolines; Cell Death; Cells, Cultured; Cerebral Cortex; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Mammalian; Excitatory Amino Acid Agonists; Glucose; Hypoxia; L-Lactate Dehydrogenase; Male; N-Methylaspartate; Neurons; Neuroprotective Agents; Organ Culture Techniques; Rats; Rats, Wistar; Retina

Since it has to be expected that individuals exposed to oxidative stress who take supplements of beta-carotene are simultaneously exposed to both beta-carotene cleavage products (CPs) and oxidative stress, and both exposures have been demonstrated to cause genotoxic effects in primary rat hepatocytes, cyto- and genotoxic effects on primary rat hepatocytes after supplementation of the medium with increasing concentrations of a CP mixture during exposure to oxidative stress by treatment with either DMNQ (2,3-dimethoxy-1,4-naphthoquinone) or hypoxia/reoxygenation (Hy/Reox) was investigated. The cytological endpoints analysed were the mitotic indices, the percentages of apoptotic and necrotic cells, the percentages of micronucleated (MN) cells and the number of chromosomal aberrations (CAs) and sister chromatid exchanges (SCE). The results obtained clearly demonstrate that the CP mixture enhances the genotoxic effects of oxidative stress exposure, whereas it had no effect at all on the endpoints of cytotoxicity studied. These results further support the hypothesis that CP might be responsible for the reported carcinogenic response in the beta-CArotene and Retinol Efficacy Trial (CARET) and Alpha-Tocopherol Beta-carotene Cancer prevention (ATBC) chemoprevention trials.

Topics: Animals; beta Carotene; Chromosome Aberrations; DNA Damage; Dose-Response Relationship, Drug; Female; Hepatocytes; Hypoxia; Metaphase; Naphthoquinones; Oxidative Stress; Oxygen; Rats; Rats, Inbred F344

Hypoxia is known to induce oxidative stress in organisms leading to tissue injury. In the present study beta-carotene (BC) given at 10 mg/kg body weight (BW) in reducing the oxidative stress induced by hypoxia was evaluated on male albino rats. Hypoxia exposure caused an increase in malondialdehyde (MDA) levels in plasma and tissues, a concurrent decrease in blood glutathione (GSH), glutathione peroxidase (GPx), plasma protein and plasma BC content. Hemoglobin concentration, Red blood corpuscles (RBC) and White blood corpuscles (WBC) count were also increased under hypoxia. BC supplementation reversed the trend, inducing a significant decrease (P<0.05) in MDA and subsequent increase in plasma and tissue GSH levels in animals exposed to hypoxia. Blood GPx and plasma protein also increased significantly in BC supplemented animals. BC supplementation did not alter the changes in Hb concentration, RBC and WBC count. BC has potent antioxidant activities in reducing the oxidative stress induced by hypobaric hypoxia.

Topics: Animals; Antioxidants; beta Carotene; Drug Evaluation, Preclinical; Glutathione; Hypoxia; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley

2-Oxoglutarate-supported rat liver mitochondria were loaded with moderate amounts of calcium and submitted to O2 deprivation and reoxygenation. In the presence of acetoacetate, anaerobic energy production maintained Ca2+ retention by mitochondria during the anoxia period unless the Pi concentration of the incubation solution was raised to 4-6 mM. Acetoacetate prompted Ca2+ release from O2-deprived mitochondria at elevated Pi levels, presumably due to occurrence of a permeability transition of the inner membrane. Providing 3-hydroxybutyrate and malate, together with acetoacetate, was found to delay the permeability transition until O2 was reintroduced, i.e., O2 triggered a paradoxical release of Ca2+ from mitochondria under these conditions. Whether initiated by O2 in the presence of Pi or by Pi under aerobic conditions, Ca2+ release was initially activated and subsequently inhibited or reversed in the presence of alpha-tocopherol (10-90 mumol.g protein-1). Similar effects were exerted by alpha-tocopherol during Pi-induced Ca2+ release from oligomycin-treated mitochondria supported by succinate (+ rotenone). In addition, the permeability transition was delayed by retinol (3-30 mumol.g protein-1) while beta-carotene, ubiquinone, and water-soluble antioxidants, including Trolox C, were ineffective. Other observations suggest that the Ca(2+)-releasing and/or -retaining effects of alpha-tocopherol and retinol may be independent from pro- and/or antioxidant activities. Effects resembling those of alpha-tocopherol were exerted by alpha-tocopherol succinate, which is devoid of antioxidant activity. Our data indicate that the permeability transition of Ca(2+)-loaded liver mitochondria may be triggered by O2, in the presence of ketone bodies, and affected by lipid-soluble antioxidants through mechanisms seemingly unrelated to free-radical generation or scavenging.

Topics: Acetoacetates; Anaerobiosis; Animals; Antioxidants; beta Carotene; Calcium; Carotenoids; Chromans; Hypoxia; Kinetics; Mitochondria, Liver; Oligomycins; Oxygen; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Ubiquinone; Vitamin A; Vitamin E