Treatment Of Oxidative Stress Research Articles

Oxido-Reduction Potential as a Method to Determine Oxidative Stress in Semen Samples.

There are different estimates for the incidence of infertility. Its occurrence may vary from area to area, but on average, it affects 15% of couples and 10-12% of men worldwide. Many aspects of infertility can be linked to reactive oxygen species (ROS) and the process of oxidative stress (OS). The association between poor semen quality and OS is well known. Unfortunately, there is no accepted protocol for the diagnosis and treatment of OS in andrology. Oxido-reduction potential (ORP) measurement is a new method for determining the ratio between oxidant and antioxidant molecules. Currently, ORP measurement is one of the fastest and most user-friendly methods of andrological OS determination and our goals were to confirm published correlations between ORP values and sperm parameters, examine how sperm concentration influences these results, and investigate whether intracellular ROS formations are also manifested in the ORP values or not after artificial ROS induction. Intracellular ROS formations were induced by menadione (superoxide anion inducer), hydrogen peroxide, and tert-butyl hydroperoxide (lipid peroxidation inducer) treatments; sperm parameters like motility and viability were determined with an SCA Scope system, and ORP changes were recorded by the Mioxsys system. Significant correlations were noticed among the ORP, spermatozoa concentration, motility, progressive motility, and viability. Nevertheless, only the ORP value after normalization with the sperm count correlated with these parameters. Due to normalization, very low and very high sperm concentrations can give misleading results. The means of the non-normalized ORP values were almost the same. All of the applied treatments resulted in decreases in the viability, motility, and progressive motility, and interestingly, altered ORP levels were detected. In addition, it was determined that seminal plasma had a significant protective effect on spermatozoa. The elimination of seminal plasma caused higher sensitivity of spermatozoa against used OS inducers, and higher ORP levels and decreased viabilities and motilities were measured. The ORP level could be a good indicator of male OS; however, in cases of low and high sperm counts, its result can be misleading. Overall, the conclusion can be drawn that ORP determination is a suitable method for detecting intracellular ROS accumulation, but it has limitations that still need to be clarified.

Eriocitrin Alleviates Inflammation and Oxidative Stress in Subarachnoid Hemorrhage by Regulating DUSP14.

Inflammation and oxidative stress (OS) are major causes of aneurysmal subarachnoid hemorrhage (aSAH)-induced early brain injury (EBI). Eriocitrin (EC), a flavonoid compound, has anti-inflammatory and antioxidant actions. However, there is still no relevant studies on the role of EC in SAH. Accordingly, this research aims to clarify the anti-OS and anti-inflammatory efficacy of EC in SAH. Rat SAH model was established in vivo and administered with Eriocitrin (25 mg/kg). In vitro, BV2 cells were exposed to oxyhemoglobin (OxyHb) for 24 hours and pretreated with Eriocitrin (1 uM/mL, 2 uM/mL, 4 uM/mL) for 30 minutes. Water maze experiments and neurological function scores were conducted to assess cognitive and motor function. TdT-mediated dUTP Nick-End Labeling (TUNEL) staining was used to detect cortical cell apoptosis. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) were used to detect the inflammatory factors and malondialdehyde (MDA), as well as the expression of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px). Western blots were used to semi quantify nuclear factor erythroid-2-related factor 2 (Nrf2), nuclear factor-κB (NF-κB), dual specificity phosphatase 14 (DUSP14) expression. The findings suggest that EC (25 mg/kg) reduced SAH-induced central nervous system (CNS) damage, neuronal apoptosis, inflammatory reactions and OS. Regarding a mechanistic study, EC enhanced Nrf2 and NF-κB by increasing DUSP14 activation, thereby reducing the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6. In addition, EC decreased MDA while markedly elevating SOD and enhancing GSH-px. Furthermore, specifically inhibiting DUSP14 expression via using protein-tyrosine-phosphatase (PTP) inhibitor IV, neutralized the protective action of EC and aggravated inflammation and OS. In vitro experiments of OxyHb-induced BV2 cells revealed that EC promoted Nrf2 while markedly suppressing NF-κB by increasing DUSP14 activation, thereby reducing the concentrations of the above inflammatory cytokines. Moreover, EC decreased MDA while evidently increasing SOD and GSH-px. In summary, this paper lays a theoretical grounding for EC treatment of SAH-induced inflammatory reactions and OS by regulating DUSP14.

Targeting Oxidative Stress in Intracerebral Hemorrhage: Prospects of the Natural Products Approach.

Intracerebral hemorrhage (ICH), the second most common subtype of stroke, remains a significant cause of morbidity and mortality worldwide. The pathological mechanism of ICH is very complex, and it has been demonstrated that oxidative stress (OS) plays an important role in the pathogenesis of ICH. Previous studies have shown that OS is a therapeutic target after ICH, and antioxidants have also achieved some benefits in the treatment of ICH. This review aimed to explore the promise of natural products therapy to target OS in ICH. We searched PubMed using the keywords “oxidative stress in intracerebral hemorrhage” and “natural products in intracerebral hemorrhage”. Numerous animal and cell studies on ICH have demonstrated the potent antioxidant properties of natural products, including polyphenols and phenolic compounds, terpenoids, alkaloids, etc. In summary, natural products such as antioxidants offer the possibility of treatment of OS after ICH. However, researchers still have a long way to go to apply these natural products for the treatment of ICH more widely in the clinic.

Do low molecular weight antioxidants contribute to the Protection against oxidative damage? The interrelation between oxidative stress and low molecular weight antioxidants based on data from the MARK-AGE study

A redox steady state is important in maintaining vital cellular functions and is therefore homeostatically controlled by a number of antioxidative agents, the most important of which are enzymes. Oxidative Stress (OS) is associated with (or/and caused by) excessive production of damaging reactive oxygen and/or nitrogen species (ROS, RNS), which play a role in many pathologies. Because OS is a risk factor for many diseases, much effort (and money) is devoted to early diagnosis and treatment of OS. The desired benefit of the “identify (OS) and treat (by low molecular weight antioxidants, LMWA)” approach is to enable selective treatment of patients under OS. The present work aims at gaining understanding of the benefit of the antioxidants based on interrelationship between the concentration of different OS biomarkers and LMWA. Both the concentrations of a variety of biomarkers and of LMWA were previously determined and some analyses have been published by the MARK-AGE team. For the sake of simplicity, we assume that the concentration of an OS biomarker is a linear function of the concentration of a LMWA (if the association is due to causal relationship). A negative slope of this dependence (and sign of the correlation coefficient) can be intuitively expected for an antioxidant, a positive slope indicates that the LMWA is pro-oxidative, whereas extrapolation of the OS biomarker to [LMWA] = 0 is an approximation of the concentration of the OS biomarker in the absence of the LMWA. Using this strategy, we studied the effects of 12 LMWA (including tocopherols, carotenoids and ascorbic acid) on the OS status, as observed with 8 biomarkers of oxidative damage (including malondialdehyde, protein carbonyls, 3-nitrotyrosine). The results of this communication show that in a cross-sectional study the LMWA contribute little to the redox state and that different “antioxidants” are very different, so that single LMWA treatment of OS is not scientifically justified assuming our simple model. In view of the difficulty of quantitating the OS and the very different effects of various LMWA, the use of the “identify and treat” approach is questionable.

Morphine Induces Apoptosis, Inflammation, and Mitochondrial Oxidative Stress via Activation of TRPM2 Channel and Nitric Oxide Signaling Pathways in the Hippocampus.

Morphine as an opioid is an important drug in the treatment of moderate to severe pain. Several stress factors via generation of nitric oxide (NO) and oxidative stress (OS) are responsible for the adverse effects of morphine-induced analgesia, addiction, and antinociceptive tolerance, including altered Ca2+ concentration, inflammation, OS, and release of apoptotic factors. TRPM2 is a Ca2+-permeable cation channel and it is activated by OS and NO. Hence, adverse effect of morphine addiction may occur via the OS and NO-induced TRPM2 activation. Because of the unclear etiology of morphine-induced adverse effects in the hippocampus, investigating the involvement of TRPM2 and NO synthetase (NOS) activations in the treatment of morphine-induced OS, apoptosis, and neuroinflammation is a major challenge. The hippocampal neuron of TRPM2 wild-type (TRPM2-WT) and knockout (TRPM2-KO) mice were divided into control, morphine, NOS inhibitor (L-NAME) + morphine, and TRPM2 channel blockers (ACA and 2-APB) + morphine. The morphine-induced increases of apoptosis, neurondeath, OS, lipid peroxidation, caspase-3 and caspase-9, neuroinflammatory cytokines (IL-1β, TNF-α, IL-6), and Ca2+ levels in the hippocampal neuron of TRPM2-WT mouse were decreased by the L-NAME, ACA, and 2-APB treatments, although cell viability, neuron count, and reduced glutathione and glutathioneperoxidase levels were increased by the treatments. However, the effects of morphine were not observed in the hippocampus of TRPM2-KO mice. Taken together, our data show that neurodegeneration adverse effects of morphine were induced by activation of TRPM2, and excessive generations of NO and OS. Thus, inhibition of TRPM2 may modulate morphine-induced neurodegeneration in the hippocampus.

Vitamin E effect in a rat model of toluene diisocyanate-induced asthma.

Background and aimThe aim of the study was to evaluate vitamin E effect upon oxidative stress associated with toluene −2, 4-diisocyanate (TDI)-induced asthma in rats.MethodsThe five study groups were: control, vehicle, TDI, vehicle+E, TDI+E. TDI animals were sensitized by nasal administration of TDI 10% (5μl/nostril) between days 1–7 and 15–21. Between days 22–28 groups TDI+E and vehicle+E rats received vitamin E (50 mg/kg, i. v.), and control, vehicle and TDI groups received saline solution. On day 29 the rats were challenged by intranasal application of 5% TDI (5 μl/nostril). On day 30 blood, BALF and lung biopsy were harvested. Oxidative stress tests were malondialdehyde (MDA), protein carbonyls (PC), total thiols (tSH), 1,1-diphenyl-2-picryl hydrazyl (DPPH) and reduced glutathione (GSH).ResultsTDI sensitization increased oxidative stress systemically, but also locally in the respiratory airways and lung tissue. There was an increase of MDA and PC formation associated with a deficiency of the antioxidant defense reflected by DPPH decreases. There were no differences between systemic and local lung concentrations of oxidized molecules.After vitamin E treatment oxidative stress was reduced mostly due to serum, BALF and lung tissue GSH and DPPH increase.ConclusionThe study showed that in rat TDI-induced asthma there was oxidative stress caused by increased ROS production and antioxidants deficiency, and vitamin E reduced ROS production and improved antioxidant defense.

Resveratrol-loaded Nanoparticles Induce Antioxidant Activity against Oxidative Stress.

Resveratrol acts as a free radical scavenger and a potent antioxidant in the inhibition of numerous reactive oxygen species (ROS). The function of resveratrol and resveratrol-loaded nanoparticles in protecting human lung cancer cells (A549) against hydrogen peroxide was investigated in this study. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay was performed to evaluate the antioxidant properties. Resveratrol had substantially high antioxidant capacity (trolox equivalent antioxidant capacity value) compared to trolox and vitamin E since the concentration of resveratrol was more than 50 μM. Nanoparticles prepared from β-lactoglobulin (β-lg) were successfully developed. The β-lg nanoparticle showed 60 to 146 nm diameter in size with negatively charged surface. Non-cytotoxicity was observed in Caco-2 cells treated with β-lg nanoparticles. Fluorescein isothiocynate-conjugated β-lg nanoparticles were identified into the cell membrane of Caco-2 cells, indicating that nanoparticles can be used as a delivery system. Hydrogen peroxide caused accumulation of ROS in a dose- and time-dependent manner. Resveratrol-loaded nanoparticles restored H2O2-induced ROS levels by induction of cellular uptake of resveratrol in A549 cells. Furthermore, resveratrol activated nuclear factor erythroid 2-related factor 2-Kelch ECH associating protein 1 (Nrf2-Keap1) signaling in A549 cells, thereby accumulation of Nrf2 abundance, as demonstrated by western blotting approach. Overall, these results may have implications for improvement of oxidative stress in treatment with nanoparticles as a biodegradable and non-toxic delivery carrier of bioactive compounds.

Is the age-related macular degeneration (AMD) vascular disease, part of vasculopathy, respectively? Novel considerations on AMD arising from the newest pathophysiological, clinical and clinical- pharmacological observations (Preliminary Communication)

Is the age-related macular degeneration (AMD) vascular disease, part of vasculopathy, respectively? Novel considerations on AMD arising from the newest pathophysiological, clinical and clinical- pharmacological observations (Preliminary Communication)

Alpha-Linolenic Acid–Rich Wheat Germ Oil Decreases Oxidative Stress and CD40 Ligand in Patients With Mild Hypercholesterolemia

Epidemiological studies have underlined that a higher intake of α-linolenic acid (18:3n-3) is inversely associated with coronary and carotid atherosclerotic disease.1 Long-chain n-3 fatty acids have been suggested to delay the atherosclerotic process through an antiinflammatory activity2 and in turn to stabilize vulnerable plaque.3 Previous studies suggested, in particular, that n-3 fatty acids may exert an antiinflammatory action by reducing oxidative stress.4 As we have previously shown that oxidative stress is implicated in upregulating CD40 ligand (CD40L), a protein with inflammatory and prothrombotic property,5,6 we tested the hypothesis that 18:3n-3 may protect against atherosclerotic disease also via inhibiting oxidative stress–mediated CD40L expression. To investigate this issue, 32 patients with hypercholesterolemia were randomly allocated, in a double blind fashion, to 2 months supplementation with 2 vegetable oils (1 tbsp/d) containing low (maize oil, 0.63%) or high (wheat germ oil, 8.6%) percentage of 18:3n-3. Before and after treatment oxidative stress and CD40L, a protein that is implicated in the progression of atherosclerotic disease,5 were measured. Also, we analyzed in vitro whether 18:3n-3 …

(salen)MnIII Compounds as Nonpeptidyl Mimics of Catalase. Mechanism-Based Tuning of Catalase Activity: A Theoretical Study

We present the results of the first theoretical investigation of salen-manganese complexes as synthetic catalytic scavengers of hydrogen peroxide molecules that mimic catalase enzymes. Catalase mimics can be used as therapeutic agents against oxidative stress in treatment of many diseases, including Alzheimer's disease, stroke, heart disease, aging, and cancer. A ping-pong mechanism approach has been considered to describe the H2O2 dismutation reaction. The real compounds reacting with a peroxide molecule were utilized in our BP density functional calculations to avoid uncertainties connected with using incomplete models. Part I of the dismutation reaction-converting a peroxide molecule into a water molecule with simultaneous oxidation of the metal atom of the catalyst-can be done quite effectively at the Mn catalytic center. To act as catalytic scavengers of hydrogen peroxide, the oxomanganese salen complexes have to be deoxidized during part II of the dismutation reaction. It has been shown that there are two possible reaction routes for the second part of the dismutation reaction: the top and the side substrate approach routes. Our results suggest that the catalyst could be at least temporarily deactivated (poisoned) in the side approach reaction route due to the formation of a kinetically stable intermediate. Overall, the side approach reaction route for the catalyst recovery is the bottleneck for the whole dismutation process. On the basis of the detailed knowledge of the mode of action of the (salen)MnIII catalase mimics, we suggest and rationalize structural changes of the catalyst that should lead to better therapeutic properties. The available experimental data support our conclusions. Our findings on the reaction dismutation mechanism could be the starting point for further improvement of salen-manganese complexes as synthetic catalytic scavengers of reactive oxygen species.

(Salen)Mn(III) Compound as a Nonpeptidyl Mimic of Catalase: DFT Study of the Metal Oxidation by a Peroxide Molecule

Catalase mimics can be used as therapeutic agents against oxidative stress in treatment of many diseases, including Alzheimer's disease, stroke, heart disease, aging, and cancer. (Salen)Mn(III) compounds have been proven to be promising as synthetic antioxidants that, in particular, dismutate H2O2, resulting in two water molecules and oxygen. An understanding of the mechanism of the dismutation process is an important basis for rational design and tuning these analogues to yield better therapeutic properties. In addition, the study of the catalytic mechanism of the functional biomimetics of enzymes might contribute to a better understanding of the complex enzymatic activities for the corresponding biological compounds. For the first time, using the density functional theory method, we have performed a quantum chemical investigation of the catalase activity of the (salen)Mn(III) compound. The real compound reacting with a peroxide molecule has been utilized in the calculations to avoid uncertainties connec...