Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe最新文献

Living organisms are prone to different types of nanomaterials and the interaction leads to biochemical alteration depending on the dose of received nanomaterials. At an average dose, nanoparticles cause toxicity, and they may induce oxidative stress by shifting the oxidoreduction equilibrium. Using a relatively low dose, nanoparticles can be beneficial in nanomedicine to correct deficiencies of essential elements. Moreover, nanoparticles can serve as carriers to deliver entrapped drugs through complex physiological media and finally reach the target organs or cells and release the drugs. Living cells have developed various strategies to nullify the effects of nanoparticles beyond their normal amount and release the key components retained by these particles. This review is focused on the nanoparticles' effects screening and investigates the correction of the nanotoxicity by the reported protective agents to make the use of nanoparticles safer. The model of this study concerns the brain as a highly sensitive organ and well protected by the blood barrier.

Exercise activates the metabolic system in skeletal muscles, which is modulated by antioxidant supplementation. Some antioxidants such as glutathione accelerate metabolic adaptation induced by exercise training, whereas other antioxidants such as vitamin C suppress it. Thus, the present study aimed to elucidate the effects of oral administration of glutathione and vitamin C on metabolic and redox responses after acute exercise in mice. ICR mice were randomly divided into sedentary, exercise, exercise with glutathione, and exercise with vitamin C groups. In the exercise groups, mice were subjected to treadmill running at 30 m/min for 30 min. Immediately after exercise, glutathione (2% w/v, 5uL/g body weight) or vitamin C (10% w/v, 5uL/g body weight) were administered. Gastrocnemius muscle and plasma samples were collected at 3 h post-exercise. We found that plasma creatine kinase levels were only elevated in the exercise group. Malondialdehyde levels in skeletal muscle were elevated after exercise, but this elevation was suppressed by glutathione administration. PGC-1α expression was increased in both the exercise and glutathione groups compared with the sedentary group; however, the expressions of its downstream proteins were only increased in the glutathione group. Reduced glutathione form was notably increased in the mitochondria, whereas oxidized glutathione was significantly increased in the cytosol of the glutathione administration group compared with the exercise group. Thioredoxin reductase activity was also higher in the glutathione group than in the sedentary and exercise groups. Thus, this study demonstrates that post-exercise glutathione administration accelerates the exercise-induced responses of mitochondrial factors in skeletal muscle, which may be mediated by the modulation of the redox system.

The maintenance of balance between pro-oxidants and antioxidants is paramount for healthy aerobic cell status as cell may face oxidative stress if this balance is disturbed. During ascent to high altitude, reactive oxygen species (ROS) is enhanced and antioxidant system declined due to low oxygen availability. A number of evidences suggested the role of high altitude hypoxia in various maladies due to perturbed redox homeostasis. High altitude associated maladies include High Altitude Pulmonary Edema (HAPE), High Altitude Cerebral Edema (HACE), Acute mountain sickness (AMS), chronic mountain sickness (CMS), pulmonary hypertension, venous thrombosis, sleep disorders, muscle atrophy etc. Many supplementations such as vitamin C, vitamin E, resveratrol, β-carotene, quercetin, acetyl-l-carnitine, Ginkgo biloba, N-acetyl cysteine, selenium, Ganoderma lucidum, l-carnosine, ursolic acid have been extensively researched for counteracting the high altitude associated oxidative stress. However, most of the supplementations are having limited beneficial effects. However, miRNA can become an answer for high altitude associated pathophysiological conditions as miRNAs regulate energy metabolism, metabolic pathways, oxidative stress, inflammation etc. On that, miRNAs are easily assessable, highly specific and sensitive small molecules that can also exploited as a biomarker. To consider the seriousness of the problem, the present study screened out the miRNAs that are directly involved in maintaining NADPH oxidases (NOX), nitric oxide synthases (NOS), thioredoxin induced protein (TXNIP) and antioxidants enzymes, comprising superoxide dismutase (SOD), catalase, glutathione peroxidise (GPX), peroxiredoxins (PRDX), thioredoxins (TXN), thioredoxin reductase (TXNRD). After analysis with the screened miRNAs, the extraction of miRNA (12 miRNAs) was done that have role in regulating free radical producing enzymes such as NOS, NOX and TXNIP. It is hypothesized that regulating miRNAs could become a probable answer for high altitude associated maladies. Hence, further research in this direction is required to proof the concept.

Therapeutic use of alternative nitric oxide (NO) sources, such as nitrite and nitrate may be a protective influence on pulmonary vasculature abnormalities.

Aim

To evaluate whether the maternal administration of nitrite prevents the morphological and molecular changes that affect the pulmonary arterioles of congenital diaphragmatic hernia (CDH) neonates.

Methods

CEUA #88/2017. Sprague-Dawley neonate rats were divided into 6 groups: 1. control; 2. control + nitrite; 3. nitrofen exposed; 4. nitrofen exposed + nitrite; 5. CDH and 6. CDH + nitrite. The pregnant rats from nitrofen exposed and CDH groups were exposed to nitrofen on gestational day (GD) 9.5. The treatment with nitrite was made by gavage (15 mg/kg/day), on the last five gestational days. On GD 21.5 the fetuses were harvested. The following parameters were analyzed: lung and plasma nitrite concentration; media wall thickness (MWT) and endothelial NO synthase eNOS and inducible NO synthase iNOS immunohistochemistry of pulmonary arterioles.

Results

Nitrite treatment increased the maternal plasma concentration of nitrite in control and nitrofen-exposed rats. All neonates exposed to nitrofen showed an increase of nitrofen in the lung and plasma. Nitrite treatment decreased the MWT of pulmonary arterioles of CDH neonates. Nitrite treatment increased eNOS marker and attenuated iNOS marker in neonates with CDH.

Conclusions

Nitrite maternal treatment rescued the morphometry and recovered eNOS expression of CDH pulmonary arterioles during CDH. Nitrite is a potential prenatally therapeutic approach to vascular alterations present in CDH neonates.

Adrenaline (AD) is a naturally occurring catecholamine, synthesised in the adrenal medulla to prepare the organisms for a "fight or flight" response. Under stressful circumstances, the circulatory catecholamine undergoes auto-oxidation, resulting in the formation of free radicals. Chronic stress results in the depletion of micronutrient stores in the body. Pyridoxine, often known as vitamin B₆, is an essential water-soluble vitamin that acts as a coenzyme in many metabolic processes. Therefore, our current investigation has prioritized the regulation of pyridoxine metabolism during the period of chronic stress and the precise role of melatonin, as a natural antioxidant, in preventing the alterations generated by adrenaline in cardiac and hepatic tissues. Adrenaline augmented the oxidative stress indices, leading to an imbalance in the antioxidative state resulting in changes in the levels of certain organ-specific serum markers, modifications in the levels of PL (pyridoxal), PLP (pyridoxal-5-phosphate), and the enzymes responsible for their metabolism and breakdown. The foregoing results were corroborated by the histochemical and histological examinations. Melatonin efficiently counteracted all these harmful changes. Besides, the current study demonstrates that both PLP and melatonin show efficacy in scavenging free radicals, including superoxide anion free radicals and hydroxyl radicals, in the chemical system. However, the in vitro studies demonstrated that when administered together, melatonin and PLP more effectively mitigate free radical generation than the individual molecule. These findings were further confirmed by the ITC binding study. These results suggest that a combination of melatonin and PLP could be a better therapeutic approach for the amelioration of stress induced oxidative damages in cardiac and hepatic tissues with an improved pyridoxine metabolism.

Skeletal muscle insulin resistance is pivotal in the pathogenesis of type 2 diabetes mellitus (T2DM). Oxinflammation, referred to as the coexistence of and tight relationship between inflammation and oxidative stress, along with mitochondrial dysfunction and lipotoxicity have all been implicated in the pathogenesis of skeletal muscle insulin resistance. Most importantly, these effectors of insulin resistance are able to fuel one another, thereby generating a complex vicious cycle. This review aims at providing an updated and critical overview on the intimate cross-talk between oxinflammation, mitochondrial dysfunction and lipotoxicity as key molecular mechanisms underpinning insulin resistance. Additionally, the role of dietary fatty acids in modulating the key actors of this vicious cycle and the repercussions on skeletal muscle insulin sensitivity will be discussed in detail.

Cellular metabolic activities are controlled by pathways catalyzed by enzymes, closely regulated by signal transduction through induction or inhibition processes. Metabolic disorders and cellular dysregulation are often linked to redox-dependent signaling in a complex relationship. Glutathione (GSH) and polyphenols which are known regulators of cellular redox homeostasis have been studied immensely. However, no study has considered their potential interactions and synergies as novel mechanisms to control cellular disorders. GSH does not only act as an antioxidant, but as a ligand that binds to inactivate enzymes and toxins. Also, depending on cellular environment, structure, pH, concentration and availability of transition metals of high charge density, polyphenols may possess either anti-oxidant or pro-oxidant properties. Owing to their remarkable influence on cellular redox potential and metabolic signaling as individual compounds, this study considered the potential interactions and synergies between GSH and polyphenols in disease management. Generally, both GSH and polyphenols reduce oxidative stress in normal cells and may under exacerbating conditions of low GSH/GSSG ratio, induce apoptotic mechanisms in abnormal cells. Investigating the effects of pH, polyphenol and GSH concentrations, availability of transition metals, caloric restriction and polyphenol structure on apoptosis and proliferation in cancer cells in the future may be a basis for the synergistic exploitation of GSH and polyphenols in disease management.

Individuals with a history of mild traumatic brain injury (mTBI) are at an increased risk for neurodegenerative disease, suggesting that intrinsic neuroprotective mechanisms, such as the endogenous antioxidant reservoir, may be depleted long-term after mTBI. Here, we retrospectively analyzed symptoms and blood antioxidants in patients with a history of mTBI who presented to Resilience Code, a sports medicine clinic in Colorado. Significant decreases in alpha-tocopherol, selenium, linoleic acid, taurine, docosahexaenoic acid, and total omega-3 were measured in the total mTBI population versus controls. Male mTBI patients showed depletion of a larger array of antioxidants than females. Patients with a history of mTBI also reported significantly worsened emotional, energy, head, and cognitive symptoms, with males displaying more extensive symptomology. Multiple or chronic mTBI patients had worsened symptoms than single or acute/subchronic mTBI patients, respectively. Finally, male mTBI patients with the largest reductions in polyunsaturated fatty acids (PUFAs) displayed worse symptomology than male mTBI patients with less depletion of this antioxidant reservoir. These results demonstrate that antioxidant depletion persists in patients with a history of mTBI and these deficits are sex-specific and associated with worsened symptomology. Furthermore, supplementation with specific antioxidants, like PUFAs, may diminish symptom severity in patients suffering from chronic effects of mTBI.

Mitochondrial permeability transition pore (mPTP) channel plays a central role in cell death because it mediates the effect of a sudden large opening of the inner mitochondrial membrane. Its associations with adenine nucleotide translocase and with ATP synthase within the general framework of mPTP research were challenged by genetic knock out experiments. This paper proposes the hypothesis that the matrix ATP regulates the mPTP. That hypothesis not only succeeds in classifying and explaining the existing experimental data but it also fits quite well to a peripheral branch of mPTP research proposing that the channel is composed of a combination of polyphosphates and poly-(R)-3-hydroxybutyrates glued by Ca ions. ATP also has a polyphosphate part and thus could be potentially incorporated into such kind of a channel. ATP not only has the potential to decrease the effective channel cross-section when the matrix ATP pool is full, but also, having four negative charges, ATP could be driven across the membrane, together with some accompanying metal ions. Thus, an effective potassium hydrogen exchanger is constructed. Cell death and “permeability transition” happen when the matrix ATP pool is emptied and so the mPTP channel is emptied from the ATP. As a result, the effective channel cross-section would greatly increase; instead of effectively going out, potassium would go in, and the matrix would burst. Hence, the regulation of the matrix ATP level could explain the effect of cyclosporin A – the main experimental modulator of mPTP channel activity, the mechanism of hypoxic/reperfusion injury, and many other.

SiO₂ nanoparticles functionalized with glutamate were investigated for their ability to alleviate oxidative stress caused by prolonged exposure to hydrogen peroxide (H₂O₂). The study involved ten different groups, each consisting of eight animals, to examine the effects of H₂O₂ -induced oxidative stress. The results demonstrated that exposure to H₂O₂ stress oxidative biomarkers were altered accompanied with a loss of spatial learning and memory in rats performing the Morris water maze task. Furthermore, SiO₂ nanoparticles functionalized with L-glutamic acid alleviated the H₂O₂-induced acceleration of necrotic and degenerative cell changes in the hippocampus, subiculum, caudate-putamen, and frontal cortex. Additionally, L-glutamic acid-functionalized SiO₂ nanoparticles reduced the redox imbalance and interfered with acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities induced by H₂O₂.