Similar Slow Component of Oxygen Uptake and Ventilatory Efficiency between an Aerobic Dance Session on an Air Dissipation Platform and a Constant-Load Treadmill Test in Healthy Women.

There is a lack of evidence about the slow component of oxygen consumption (V.O2sc) and ventilatory efficiency (slope VE·VCO2−1) during an aerobic dance (AD) session on an air dissipation platform (ADP) despite the key role played in endurance exercises. This research was designed to assess V.O2sc, ventilatory efficiency, and blood lactate concentration by comparing two exercise modes: AD session on an ADP versus treadmill test at a constant-load intensity of the first ventilatory threshold (VT1). In the first session, an incremental treadmill test was completed. In sessions 2 and 3, the participants were randomly assigned to the AD session on an ADP or to a treadmill constant-load test at VT1 intensity to determine their cardioventilatory responses. In addition, their blood lactate levels and ratings of perceived exertion (RPE, CR-10) were evaluated. No significant differences were found between the constant-load treadmill test and AD session on an ADP with respect to V.O2sc, VE VCO2−1 slope, and RPE (p > 0.05). Higher blood lactate concentrations were observed in an AD session on an ADP than in a constant-load treadmill test at 10 min (p = 0.003) and 20 min (p < 0.001). The two different exercise modalities showed similar V.O2sc and VE·VCO2−1 slope, even though the blood lactate concentrations were different.

Aerobic Dance on an Air Dissipation Platform Improves Cardiorespiratory, Muscular and Cellular Fitness in the Overweight and Obese Elderly.

Background: Obesity is a global health problem associated with a high number of comorbidities that decrease functional capacity, especially in elderly people. Aerobic dance is considered a viable strategy to prevent the effects of aging, mainly in obese and overweight elderly people. This study aimed to evaluate the effects of aerobic dance on an air dissipation platform (ADP) on body composition, oxidative stress and muscular and cardiorespiratory fitness in elderly people. Methods: In total, 32 elderly adults (67.1 ± 3.6) were divided into 3 groups based on body mass index: healthy (HG), overweight (OWG) and obese (OG). Training program of aerobic dance on an ADP was carried out twice a week for 12 weeks. Results: OWG (p = 0.016) and OG decreased their weight (p < 0.001). There was a significant decrease in malondialdehyde concentrations in all experimental groups (p < 0.05). OWG and OG significantly improved their peak oxygen uptake (p < 0.01). HG increased the vertical jump height (p < 0.05), and HG and OG improved the power output of the lower extremities (p < 0.05). Conclusions: The aerobic dance on an ADP may be an effective alternative to lose weight, prevent oxidative stress and improve cardiorespiratory fitness in obese and overweight elderly people.

Nrf2 and oxidative stress in liver ischemia/reperfusion injury.

In response to stress signal, nuclear factor-erythroid 2-related factor 2 (Nrf2) induces the expression of target genes involved in antioxidant defense and detoxification. Nrf2 activity is strictly regulated through a variety of mechanisms, including regulation of Keap1-Nrf2 stability, transcriptional regulation (NF-ĸB, ATF3, ATF4), and post-transcriptional regulation (miRNA), evidencing that transcriptional responses of Nrf2 are critical for the maintenance of homeostasis. Ischemia-reperfusion (IR) injury is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, the generation of reactive oxygen species (ROS) leads to damage from oxidative stress, oxidation of biomolecules, and mitochondrial dysfunction. Oxidative stress can trigger apoptotic and necrotic cell death. Stress factors also result in the assembly of the inflammasome protein complex and the subsequent activation and secretion of proinflammatory cytokines. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense against the cytotoxic effects of oxidative stress and help to promote hepatic recovery during IR. The complex crosstalk between Nrf2 and cellular pathways in liver IR injury and the potential therapeutic target of the Nrf2 inducers will be discussed in the present review.

Intermittent Hypobaric Hypoxic Preconditioning Provides Neuroprotection by Increasing Antioxidant Activity, Erythropoietin Expression and Preventing Apoptosis and Astrogliosis in the Brain of Adult Rats Exposed to Acute Severe Hypoxia.

BACKGROUND: Exposure to intermittent hypoxia has been demonstrated to be an efficient tool for hypoxic preconditioning, preventing damage to cells and demonstrating therapeutic benefits. We aimed to evaluate the effects of respiratory intermittent hypobaric hypoxia (IHH) to avoid brain injury caused by exposure to acute severe hypoxia (ASH). METHODS: biomarkers of oxidative damage, mitochondrial apoptosis, and transcriptional factors in response to hypoxia were assessed by Western blot and immunohistochemistry in brain tissue. Four groups of rats were used: (1) normoxic (NOR), (2) exposed to ASH (FiO2 7% for 6 h), (3) exposed to IHH for 3 h per day over 8 days at 460 mmHg, and (4) ASH preconditioned after IHH. RESULTS: ASH animals underwent increased oxidative-stress-related parameters, an upregulation in apoptotic proteins and had astrocytes with phenotype forms compatible with severe diffuse reactive astrogliosis. These effects were attenuated and even prevented when the animals were preconditioned with IHH. These changes paralleled the inhibition of NF-κB expression and the increase of erythropoietin (EPO) levels in the brain. CONCLUSIONS: IHH exerted neuroprotection against ASH-induced oxidative injury by preventing oxidative stress and inhibiting the apoptotic cascade, which was associated with NF-κB downregulation and EPO upregulation.

Extracellular ferritin contributes to neuronal injury in an in vitro model of ischemic stroke.

Previous clinical and experimental studies have shown that neurological decline and poor functional outcome after acute ischemic stroke in humans are associated with high ferritin levels in serum and cerebrospinal fluid (CSF) within 24 h of ischemic stroke onset. The aim of the present study was to find out if and how high extracellular ferritin concentrations can increase the excitotoxicity effect in a neuronal cortical culture model of stroke. Extracellular ferritin (100 ng/ml) significantly increased the excitotoxic effect caused by excessive exogenous glutamate (50 µM and 100 µM) by leading to an increase in lipid peroxidation, a reduction in mitochondrial membrane potential, and a decrease in neuron viability. Extracellular apoferritin (100 ng/ml), the iron-free form of the protein, does not increase the excitotoxicity of glutamate, which proves that iron was responsible for the neurotoxic effect of the exogenous ferritin. We present evidence that extracellular ferritin iron exacerbates the neurotoxic effect induced by glutamate excitotoxicity and that the effect of ferritin iron is dependent of glutamate excitotoxicity. Our results support the idea that body iron overload is involved in the severity of the brain damage caused by stroke and reveal the need to control systemic iron homeostasis.

Cardiorespiratory, Metabolic and Muscular Responses during a Video-Recorded Aerobic Dance Session on an Air Dissipation Platform.

BACKGROUND: Aerobic dance (AD) is an appropriate physical activity for improving cardiorespiratory fitness. This study aimed to compare cardiorespiratory and metabolic responses, and muscle fatigue between an air dissipation platform (ADP) and a hard surface during a video-recorded AD session. METHODS: 25 healthy young women (23.3 ± 2.5 years) completed three sessions. In session 1, participants performed an incremental test to exhaustion on a treadmill. One week after session 1, participants were randomly assigned in a crossover design to perform video-recorded AD sessions on an ADP and on a hard surface (sessions 2 and 3). Cardiorespiratory and metabolic responses were assessed during AD sessions. Muscular fatigue was measured before and after AD sessions by a countermovement jump test. RESULTS: Significantly higher heart rate, respiratory exchange ratio, pulmonary ventilation, ventilatory oxygen equivalent, and ventilatory carbon dioxide equivalent were observed on an ADP than on a hard surface (p < 0.05). Despite a significant increase in lactate levels on an ADP (p ≤ 0.01), muscular fatigue and perceived exertion rating were similar on both surfaces (p > 0.05). CONCLUSIONS: Video-recorded AD on an ADP increased the cardioventilatory and metabolic responses compared to a hard surface, preventing further muscle fatigue.

Aldehyde Dehydrogenase 2 (ALDH2) in Rat Fatty Liver Cold Ischemia Injury.

Institut George Lopez-1 (IGL-1) and Histidine-tryptophan-ketoglutarate (HTK) solutions are proposed as alternatives to UW (gold standard) in liver preservation. Their composition differs in terms of the presence/absence of oncotic agents such as HES or PEG, and is decisive for graft conservation before transplantation. This is especially so when fatty (steatotic) livers are used since these grafts are more vulnerable to ischemia insult during conservation. Their composition determines the extent of the subsequent reperfusion injury after transplantation. Aldehyde dehydrogenase-2 (ALDH2), a mitochondrial enzyme, has been reported to play a protective role in warm ischemia-reperfusion injury (IRI), but its potential in fatty liver cold ischemic injury has not yet been investigated. We evaluated the relevance of ALDH2 activity in cold ischemia injury when fatty liver grafts from Zucker Obese rats were preserved in UW, HTK, and IGL-1 solutions, in order to study the mechanisms involved. ALDH2 upregulation was highest in livers preserved in IGL-1. It was accompanied by a decrease in transaminases, apoptosis (Caspase 3 and TUNEL assay), and lipoperoxidation, which was concomitant with the effective clearance of toxic aldehydes such as 4-hydroxy-nonenal. Variations in ATP levels were also determined. The results were consistent with levels of NF-E2 p45-related factor 2 (Nrf2), an antioxidant factor. Here we report for the first time the relevance of mitochondrial ALDH2 in fatty liver cold preservation and suggest that ALDH2 could be considered a potential therapeutic target or regulator in clinical transplantation.

Ubiquitin-proteasome system and oxidative stress in liver transplantation.

A major issue in organ transplantation is the development of a protocol that can preserve organs under optimal conditions. Damage to organs is commonly a consequence of flow deprivation and oxygen starvation following the restoration of blood flow and reoxygenation. This is known as ischemia-reperfusion injury (IRI): a complex multifactorial process that causes cell damage. While the oxygen deprivation due to ischemia depletes cell energy, subsequent tissue oxygenation due to reperfusion induces many cascades, from reactive oxygen species production to apoptosis initiation. Autophagy has also been identified in the pathogenesis of IRI, although such alterations and their subsequent functional significance are controversial. Moreover, proteasome activation may be a relevant pathophysiological mechanism. Different strategies have been adopted to limit IRI damage, including the supplementation of commercial preservation media with pharmacological agents or additives. In this review, we focus on novel strategies related to the ubiquitin proteasome system and oxidative stress inhibition, which have been used to minimize damage in liver transplantation.

Preconditioning-Like Properties of Short-Term Hypothermia in Isolated Perfused Rat Liver (IPRL) System.

Hypothermia may attenuate the progression of ischemia-induced damage in liver. Here, we determined the effects of a brief cycle of hypothermic preconditioning applied before an ischemic/reperfusion (I/R) episode in isolated perfused rat liver (IPRL) on tissue damage and oxidative stress. Rats (male, 200-250 g) were anaesthetised with sodium pentobarbital (60 mg·kg-1 i.p) and underwent laparatomy. The liver was removed and perfused in a temperature-regulated non-recirculating system. Livers were randomly divided into two groups (n = 6 each group). In the hypothermia-preconditioned group, livers were perfused with hypothermic buffer (cycle of 10 min at 22 °C plus 10 min at 37 °C) and the other group was perfused at 37 °C. Both groups were then submitted to 40 min of warm ischemia and 20 min of warm reperfusion. The level of tissue-damage indicators (alanine amino transferase, ALT; lactate dehydrogenase, LDH; and proteins), oxidative stress markers (thiobarbituric acid-reactive substances, TBARS; advanced oxidation protein products, AOPP; and glutathione, GSH) were measured in aliquots of perfusate sampled at different time intervals. Histological determinations and oxidative stress biomarkers in homogenized liver (AOPP; TBARS; nitric oxide derivatives, NOx; GSH and glutathione disulphide, GSSG) were also made in the tissue at the end. Results showed that both damage and oxidant indicators significantly decreased while antioxidant increased in hypothermic preconditioned livers. In addition, homogenized liver determinations and histological observations at the end of the protocol corroborate the results in the perfusate, confirming the utility of the perfusate as a non-invasive method. In conclusion, hypothermic preconditioning attenuates oxidative damage and appears to be a promising strategy to protect the liver against IR injury.

The Relevance of the UPS in Fatty Liver Graft Preservation: A New Approach for IGL-1 and HTK Solutions.

The 26S proteasome is the central proteolytic machinery of the ubiquitin proteasome system (UPS), which is involved in the degradation of ubiquitinated protein substrates. Recently, UPS inhibition has been shown to be a key factor in fatty liver graft preservation during organ cold storage using University of Wisconsin solution (UW) and Institute Georges Lopez (IGL-1) solutions. However, the merits of IGL-1 and histidine-tryptophan-ketoglutarate (HTK) solutions for fatty liver preservation have not been compared. Fatty liver grafts from obese Zücker rats were preserved for 24 h at 4 °C. Aspartate aminotransferase and alanine aminotransferase (AST/ALT), glutamate dehydrogenase (GLDH), ATP, adenosine monophosphate protein kinase (AMPK), e-NOS, proteasome activity and liver polyubiquitinated proteins were determined. IGL-1 solution prevented ATP breakdown during cold-storage preservation of steatotic livers to a greater extent than HTK solution. There were concomitant increases in AMPK activation, e-NOS (endothelial NOS (NO synthase)) expression and UPS inhibition. UPS activity is closely related to the composition of the solution used to preserve the organ. IGL-1 solution provided significantly better protection against ischemia-reperfusion for cold-stored fatty liver grafts than HTK solution. The effect is exerted through the activation of the protective AMPK signaling pathway, an increase in e-NOS expression and a dysregulation of the UPS.

Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain.

Acute hypoxia increases the formation of reactive oxygen species (ROS) in the brain. However, the effect of reoxygenation, unavoidable to achieve full recovery of the hypoxic organ, has not been clearly established. The aim of the present study was to evaluate the effects of exposition to acute severe respiratory hypoxia followed by reoxygenation on the evolution of oxidative stress and apoptosis in the brain. We investigated the effect of in vivo acute severe normobaric hypoxia (rats exposed to 7% O2 for 6h) and reoxygenation in normoxia (21% O2 for 24h or 48h) on oxidative stress markers, the antioxidant system and apoptosis in the brain. After respiratory hypoxia we found increased levels of HIF-1α expression, lipid peroxidation, protein oxidation and nitric oxide in brain extracts. Antioxidant defence systems such as superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPx) and the reduced/oxidized glutathione (GSH/GSSG) ratio were significantly decreased in the brain. After 24h of reoxygenation, oxidative stress parameters and the anti-oxidant system returned to control values. Regarding the apoptosis parameters, acute hypoxia increased cytochrome c, AIF and caspase 3 activity in the brain. The apoptotic effect is greatest after 24h of reoxygenation. Immunohistochemistry suggests that CA3 and dentate gyrus in the hippocampus seem more susceptible to hypoxia than the cortex. Severe acute hypoxia increases oxidative damage, which in turn could activate apoptotic mechanisms. Our work is the first to demonstrate that after 24h of reoxygenation oxidative stress is attenuated, while apoptosis is maintained mainly in the hippocampus, which may, in fact, be the cause of impaired brain function.

Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats

Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10 % O2), one kept at normothermia (HN) (37 °C) and the other under deep hypothermia (HH) (central body temperature of 21-22 °C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4-HNE protein adduct amounts were significantly lower in the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia (AU)

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Subnormothermic Perfusion in the Isolated Rat Liver Preserves the Antioxidant Glutathione and Enhances the Function of the Ubiquitin Proteasome System.

The reduction of oxidative stress is suggested to be one of the main mechanisms to explain the benefits of subnormothermic perfusion against ischemic liver damage. In this study we investigated the early cellular mechanisms induced in isolated rat livers after 15 min perfusion at temperatures ranging from normothermia (37°C) to subnormothermia (26°C and 22°C). Subnormothermic perfusion was found to maintain hepatic viability. Perfusion at 22°C raised reduced glutathione levels and the activity of glutathione reductase; however, lipid and protein oxidation still occurred as determined by malondialdehyde, 4-hydroxynonenal-protein adducts, and advanced oxidation protein products. In livers perfused at 22°C the lysosomal and ubiquitin proteasome system (UPS) were both activated. The 26S chymotrypsin-like (ß5) proteasome activity was significantly increased in the 26°C (46%) and 22°C (42%) groups. The increased proteasome activity may be due to increased Rpt6 Ser120 phosphorylation, which is known to enhance 26S proteasome activity. Together, our results indicate that the early events produced by subnormothermic perfusion in the liver can induce oxidative stress concomitantly with antioxidant glutathione preservation and enhanced function of the lysosomal and UPS systems. Thus, a brief hypothermia could trigger antioxidant mechanisms and may be functioning as a preconditioning stimulus.

Fructose 1,6-Bisphosphate: A Summary of Its Cytoprotective Mechanism.

In clinical and experimental settings, a great deal of effort is being made to protect cells and tissues against harmful conditions and to facilitate metabolic recovery following these insults. Much of the recent attention has focused on the protective role of a natural form of sugar, fructose 1,6-bisphosphate (F16bP). F16bP is a high-energy glycolytic intermediate that has been shown to exert a protective action in different cell types and tissues (including the brain, kidney, intestine, liver and heart) against various harmful conditions. For example, there is much evidence that it prevents neuronal damage due to hypoxia and ischemia. Furthermore, the cytoprotective effects of F16bP have been documented in lesions caused by chemicals or cold storage, in a decrease in mortality during sepsis shock and even in the prevention of bone loss in experimental osteoporosis. Intriguingly, protection in such a variety of targets and animal models suggests that the mechanisms induced by F16bP are complex and involve different pathways. In this review we will discuss the most recent theories concerning the molecular model of action of F16bP inside cells. These include its incorporation as an energy substrate, the mechanism for the improvement of ATP availability, and for preservation of organelle membrane stability and functionality. In addition we will present new evidences regarding the capacity of F16bP to decrease oxidative stress by limiting free radical production and improving antioxidant systems, including the role of nitric oxide in the protective mechanism induced by F16bP. Finally we will review the proposed mechanisms for explaining its anti-inflammatory, immunomodulatory and neuroprotective properties.

Evaluation of Neuropathological Effects of a High-Fat Diet in a Presymptomatic Alzheimer's Disease Stage in APP/PS1 Mice.

Alzheimer's disease (AD) is currently an incurable aging-related neurodegenerative disorder. Recent studies give support to the hypotheses that AD should be considered as a metabolic disease. The present study aimed to explore the relationship between hippocampal neuropathological amyloid-ß (Aß) plaque formation and obesity at an early presymptomatic disease stage (3 months of age). For this purpose, we used APPswe/PS1dE9 (APP/PS1) transgenic mice, fed with a high-fat diet (HFD) in order to investigate the potential molecular mechanisms involved in both disorders. The results showed that the hippocampus from APP/PS1 mice fed with a HFD had an early significant decrease in Aß signaling pathway specifically in the insulin degrading enzyme protein levels, an enzyme involved in (Aß) metabolism, and α-secretase. These changes were accompanied by a significant increase in the occurrence of plaques in the hippocampus of these mice. Furthermore, APP/PS1 mice showed a significant hippocampal decrease in PGC-1α levels, a cofactor involved in mitochondrial biogenesis. However, HFD does not provoke changes in neither insulin receptors gene expression nor enzymes involved in the signaling pathway. Moreover, there are no changes in any enzymes (kinases) involved in tau phosphorylation, such as CDK5, and neither in brain oxidative stress production. These results suggest that early changes in brains of APP/PS1 mice fed with a HFD are mediated by an increase in Aß1 â€’ 42, which induces a decrease in PKA levels and alterations in the p-CREB/ NMDA2B /PGC1-α pathway, favoring early AD neuropathology in mice.

Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats.

Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10 % O2), one kept at normothermia (HN) (37 °C) and the other under deep hypothermia (HH) (central body temperature of 21-22 °C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4-HNE protein adduct amounts were significantly lower in the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia.

Oxidative stress and antioxidant activity in hypothermia and rewarming: can RONS modulate the beneficial effects of therapeutic hypothermia?

Hypothermia is a condition in which core temperature drops below the level necessary to maintain bodily functions. The decrease in temperature may disrupt some physiological systems of the body, including alterations in microcirculation and reduction of oxygen supply to tissues. The lack of oxygen can induce the generation of reactive oxygen and nitrogen free radicals (RONS), followed by oxidative stress, and finally, apoptosis and/or necrosis. Furthermore, since the hypothermia is inevitably followed by a rewarming process, we should also consider its effects. Despite hypothermia and rewarming inducing injury, many benefits of hypothermia have been demonstrated when used to preserve brain, cardiac, hepatic, and intestinal function against ischemic injury. This review gives an overview of the effects of hypothermia and rewarming on the oxidant/antioxidant balance and provides hypothesis for the role of reactive oxygen species in therapeutic hypothermia.

Deep hypothermia protects against acute hypoxia in vivo in rats: a mechanism related to the attenuation of oxidative stress.

There is growing interest in using hypothermia to prevent hypoxic damage in clinical and experimental models, although the mechanisms regulated by hypothermia are still unclear. As reactive oxygen and nitrogen species are the main factors causing cellular damage, our objective was to study the scope of hypothermia in preventing hypoxia-induced oxidative damage. We analysed systemic and hepatic indicators of oxidative stress after an acute hypoxic insult (10% oxygen in breathing air) in normothermic (37°C body temperature) and hypothermic conditions (22°C) in rats. Exposure to hypoxia resulted in tissue damage (aspartate aminotransferase increased from 54.6 ± 6.9 U l(-1) in control animals to 116 ± 1.9 U l(-1) in hypoxia, and alanine aminotransferase increased from 19 ± 0.8 to 34 ± 2.9 U l(-1)), oxidative stress (nitric oxide metabolites increased from 10.8 ± 0.4 µM in control rats to 23 ± 2.7 µM in hypoxia, and thiobarbituric reactive substances increased from 3.3 ± 0.2 to 5.9 ± 0.4 nm) and antioxidant consumption (reduced/oxidized glutathione ratio changed from 9.8 ± 0.3 to 6.8 ± 0.3). In contrast, when hypothermia was applied prior to hypoxia, the situation was reversed, with a reduction in aspartate aminotransferase (from 116 ± 1.9 in hypoxic animals to 63 ± 7.8 U l(-1) in animals exposed to hypothermia followed by hypoxia), alanine aminotransferase (from 34 ± 2.9 to 19 ± 0.9 U l(-1)), oxidative stress (nitric oxide metabolites decreased from 23 ± 2.7 to 17.8 ± 1.9 µM and thiobarbituric acid-reactive substances decreased from 5.9 ± 0.4 to 4.3 ± 0.2 nm) and antioxidant preservation (reduced/oxidized glutathione ratio changed from 6.8 ± 0.3 to 11.1 ± 0.1). Hypoxia induced a decrease in liver enzymatic antioxidant activities even during hypothermia. Both treatments, hypoxia and hypothermia, produced a similar increase in hepatic caspase-3 activity. In conclusion, hypothermia prevented the tissue damage and oxidative stress elicited by hypoxia. Our results provide new evidence concerning the protective mechanism of hypothermia in vivo.

Intermittent hypobaric hypoxia induces neuroprotection in kainate-induced oxidative stress in rats.

Severe hypoxia induces oxidative stress, which can lead to brain injury. In this study, we wanted to determine whether intermittent hypobaric hypoxia induces oxidative stress in the brain. In adult rats exposed to 380 mmHg in a hypobaric chamber for 3 h/day for 6 days, we determined the levels of malondialdehyde and nitric oxide derivatives in the brain, which indicated that there was no oxidative stress. The levels of N-acetylaspartate indicated that there was no neuronal loss or mitochondrial dysfunction and finally because apoptotic proteins such as caspase-3 and nuclear factor-kappa B (NF-κB) were not activated, apoptosis was probably not induced. The increase in the expression of erythropoietin (EPO) in the brain of rats exposed to hypoxia confirms the efficacy of the method used to induce hypoxia in the brain. Because EPO have antioxidant effects on the brain, the results suggest that intermittent hypoxia can increase the antioxidant capacity of the brain. This effect of intermittent hypoxia was studied using the systemic administration of kainate, as a model of brain oxidative stress. Kainate treatment induces oxidative stress in the brain, which is measured by an increase in lipid peroxidation and nitric oxide. Furthermore, in rats treated with kainate, both caspase-3 and NF-κB activity increased. However, in rats previously exposed to intermittent hypobaric hypoxia, 3 h per day for 6 days, the effect of kainate treatment resulted in the reduction of both oxidative stress and apoptotic activity. This study demonstrates that intermittent hypobaric hypoxia can increase brain antioxidant capacity in rats and induces neuroprotection in kainate-induced oxidative injury.

Nitric oxide as a mediator of fructose 1,6-bisphosphate protection in galactosamine-induced hepatotoxicity in rats.

Fructose 1,6-bisphosphate (F1,6BP) has been widely used as a therapeutic agent for different harmful conditions in a variety of tissues. The hypothesis of the present work was that the increase in nitric oxide production and the prevention of oxidative stress induced by exogenous F1,6BP mediate its protective effect against the hepatotoxic action of GalN. Experimental groups used were sham, F1,6BP (2g/kg bw i.p.), GalN (0.4g/kg bw i.p), l-NAME (10mg/kg bw i.v.), F1,6BP+GalN, l-NAME+GalN and l-NAME+F1,6BP+GalN. Animals were killed after 24h of bolus administration. F1,6BP induced an increase in NO and the redox ratio (GSH/GSSG) in liver. Western blot assays pointed to overexpression of liver eNOS in F1,6BP-treated rats. The hepatic injury induced by GalN increased transaminases in plasma and decreased the reduced/oxidized glutathione ratio in liver. The concomitant administration of F1,6BP reversed this damage, while the addition of l-NAME worsened the liver injury. We provided evidence that this F1,6BP-induced protection may be related to the increase in NO production through the positive modulation of eNOS, and the increase in intracellular reduced glutathione, thus providing a higher reducing capacity.