Current commentary: Can free radicals be good for you?

Oxidative stress in clinical situations - fact or fiction?

ROS: a step closer to elucidating their role in the etiology of light-induced skin disorders.

Vascular dysfunction in response to reactive oxygen species (ROS) plays an important role in the development and progression of atherosclerotic lesions. In most cells, mitochondria are the major source of cellular ROS during aerobic respiration. Under most conditions the rates of ROS formation and elimination are balanced through mechanisms that sense relative ROS levels. However, a chronic imbalance in redox homeostasis is believed to contribute to various chronic diseases, including atherosclerosis. Uncoupling protein-2 (UCP2) is a mitochondrial inner membrane protein shown to be a negative regulator of macrophage ROS production. In response to a cholesterol-containing atherogenic diet, C57BL/6J mice significantly increased expression of UCP2 in the aorta, while mice lacking UCP2, in the absence of any other genetic modification, displayed significant endothelial dysfunction following the atherogenic diet. Compared with wild-type mice, Ucp2(-/-) mice had decreased endothelial nitric oxide synthase, an increase in vascular cell adhesion molecule-1 expression, increased ROS production, and an impaired ability to increase total antioxidant capacity. These changes in Ucp2(-/-) mice were associated with increased aortic macrophage infiltration and more numerous and larger atherosclerotic lesions. These data establish that in the vasculature UCP2 functions as an adaptive antioxidant defense to protect against the development of atherosclerosis in response to a fat and cholesterol diet.

1 - What are Free Radicals?

Free oxygen radicals such as superoxide anion (O2¯), hydrogen peroxide (H2O2), hypochlorite (OHCl), and hydroxyl radical (OH) are called reactive oxygen species (ROS). Free radicals have a very short half-life and are continuously produced, mainly by white blood cells (WBC) and especially by granulocytes and abnormal sperm. Excessive amounts of ROS impair sperm quality. ROS levels can be measured with the chemiluminescence method using luminol as a probe.

Nanotechnology offers unique advantages over small-molecule drugs by delivering a high payload of photosensitizers to the target tissue, providing flexibility in the excitation wavelengths, enabling longer retention in the target tissue, possessing regenerative reactive oxygen speciesproducing capability and stimulating the immune system.

Protein Oxidation in Aging, Disease, and Oxidative Stress

Neurological disorders include a variety of conditions, including Alzheimer's disease, motor neuron disease and Parkinson's disease, affecting longevity and quality of life, and their pathogenesis is associated with oxidative stress. Several of the chronic neurodegenerative pathologies of the CNS share some common features, such as oxidative stress, inflammation, synapse dysfunctions, protein misfolding and defective autophagia. Neuroinflammation can involve the activation of mast cells, contributing to oxidative stress, in addition to other sources of reactive oxygen species. Antioxidants can powerfully neutralize reactive oxygen species and free radicals, decreasing oxidative damage. Antioxidant genes, like the manganese superoxide dismutase enzyme, can undergo epigenetic changes that reduce their expression, thus increasing oxidative stress in tissue. Alternatively, DNA can be altered by free radical damage. The epigenetic landscape of these genes can change antioxidant function and may result in neurodegenerative disease. This imbalance of free radical production and antioxidant function increases the reactive oxygen species that cause cell damage in neurons and is often observed as an age-related event. Increased antioxidant expression in mice is protective against reactive oxygen species in neurons as is the exogenous supplementation of antioxidants. Manganese superoxide dismutase requires manganese for its enzymic function. Antioxidant therapy is considered for age-related neurodegenerative diseases, and a new mimetic of a manganese superoxide dismutase, avasopasem manganese, is described and suggested as a putative treatment to reduce the oxidative stress that causes neurodegenerative disease. The aim of this narrative review is to explore the evidence that oxidative stress causes neurodegenerative damage and the role of antioxidant genes in inhibiting reactive oxygen species damage. Can the neuronal environment of oxidative stress, causing neuroinflammation and neurodegeneration, be reduced or reversed?

Molecular oxygen is toxic for anaerobic organisms but it is also obvious that oxygen is poisonous to aerobic organisms as well, since oxygen plays an essential role for inducing molecular damage. Molecular oxygen is a triplet radical in its ground-stage (.O-O.) and has two unpaired electrons that can undergoes consecutive reductions of one electron and generates other more reactive forms of oxygen known as free radicals and reactive oxygen species. These reactants (including superoxide radicals, hydroxyl radicals) possess variable degrees of toxicity. Nitric oxide (NO•) contains one unpaired electron and is, therefore, a radical. NO• is generated in biological tissues by specific nitric oxide synthases and acts as an important biological signal. Excessive nitric oxide production, under pathological conditions, leads to detrimental effects of this molecule on tissues, which can be attributed to its diffusion-limited reaction with superoxide to form the powerful and toxic oxidant, peroxynitrite.Reactive oxygen and nitrogen species are molecular “renegades”; these highly unstable products tend to react rapidly with adjacent molecules, donating, abstracting, or even sharing their outer orbital electron(s). This reaction not only changes the target molecule, but often passes the unpaired electron along to the target, generating a second free radical, which can then go on to react with a new target amplifying their effects.This review describes the mechanisms of oxidative damage and its relationship with the most highly studied neurodegenerative diseases and the roles of melatonin as free radical scavenger and neurocytoskeletal protector.

In addition to being the energy powerhouse of the cell, mitochondria are an important source of reactive oxygen species (ROS) during the process of molecular oxygen metabolism. Mitochondrial ROS are closely associated with normal physiological functions as well as human diseases, and participate in cell signaling, nucleic acid and protein damage, and oxidative stress induction. However, the complicated interplay between mitochondrial ROS and the cellular pathological state has not been fully elucidated. It is expected that research on the mitochondrial ROS undertaking in the molecular pathogenesis of human diseases would benefit from development of efficient tools for the detection of these ROS. In recent years, an increasing number of fluorescent probes for mitochondrial ROS with high sensitivity and selectivity have been developed. Here, we present a review of the recent advances in small molecular fluorescent probes for selective detection of ROS inside the mitochondria. In this review, the design, synthesis, characteristics, and applications of the published fluorescent probes for mitochondrial ROS are discussed in detail.

Free radical aspects of Xanthomonas campestris cultivation with liquid phase oxygen supply strategy

Today breast cancer represents the most frequent of all cancer pathologies in the world, with more than one million newly diagnosed cases and about 370000 cancer-related deaths in women each year, even with all the significant progress in its diagnosis and treatment (Ott et al., 2011). The development of breast tumor is a multistep process. It is generally thought that the initiation of breast cancer occurs after accumulation of genetic alterations that result in either activation of oncogenes and/or inactivation of tumor suppressor genes, leading to an abnormal cellular proliferation and promoting the development of tumor in mammary gland. A number of risk factors such as reproductive and hormonal factors, alcohol consumption, cigarette smoking, dietary factors and chronic inflammation have been identified for breast cancer, whose mechanisms by which they increase risk of the disease are not always clear (Mitrunen and Hirvonen, 2003). It has been proposed that the production of reactive oxygen species (ROS) leading to an oxidative stress is the linking factor between these carcinogens. The oxidative stress is defined as an imbalance between production of ROS, and their elimination by antioxidant defense system (redox imbalance). This imbalance leads to damage of important biomolecules and cells, with potential impact on the whole organism. ROS are products of a normal cellular metabolism and play vital roles in the stimulation of signalling pathways in cells in response to changes in intraand extracellular environmental conditions. During endogenous metabolic reactions, aerobic cells produce ROS such as superoxide anion (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (OH•), and organic peroxides as normal products of the biological reduction of molecular oxygen. Most ROS are generated in cells by the mitochondrial respiratory chain. Under hypoxic conditions following reoxygenation, the electron transfer at the level of complex III of mitochondrial respiratory chain to molecular oxygen occurs directly, leading to a high level of ROS. Beside oxidative phosphorylation, low levels of ROS are continuously formed by oxidase activities in peroxisomes, and by the cytochrome P450 system in endoplasmic reticulum. ROS as OH• is produced in vivo in the presence of reduced transition metals (ions of Fe, Cu) mainly via the Fenton reaction in contact with H2O2. Under normal metabolic conditions, these ROS are eliminated rapidly in normal cells by the antioxidant defense system. However, ROS may be overproduced when normal cells are exposed to a sustained environmental stress, including ionizing radiation and many

Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a naturally occurring flavonoid, was found to prevent human dermal fibroblast cell damage induced by reactive oxygen species such as hydrogen peroxide (H2O2), tert-butyl hydroperoxide (BuOOH) and superoxide anions (.O2-) in a concentration-dependent manner, and was more effective than the iron chelator, deferoxamine, hydroxyl radical (.OH) scavengers such as dimethyl sulfoxide (DMSO) and ethanol (EtOH), the lipid peroxidation chain blocker, alpha-tocopherol (Vit. E) and the xanthine oxidase inhibitor, allopurinol. To probe the mechanism of cell defense, the reaction of baicalein with oxygen free radicals was investigated using electron spin resonance (ESR) spectrometry. Baicalein decreased the signal intensities due to the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin adducts of .OH, .O2- and tert-butyl peroxyl (BuOO.) radicals in a concentration-dependent manner. The IC50 values, which are the 50% inhibition concentrations of baicalein for the free radicals, were 10, 45 and 310 microM, respectively. These results suggested that baicalein possesses free radical scavenging ability which prevents the fibroblast damage induced by these free radical species.

Molecular oxygen (O2) is essential in all species for the production of energy within mitochondria; a process known as oxidative phosphorylation. The end products of this process include adenosine triphosphate (ATP), water (H2O) and carbon dioxide (CO2). In addition, very small amounts of reactive oxygen species (ROS) or free radicals are continuously produced as a consequence of normal metabolism of oxygen but which, on occasions when they become overabundant, may toxically damage cells, and therefore need to be biochemically neutralized or extruded from cells. Antioxidants are defined as substances capable of delaying or inhibiting production of ROS intermediates. Cells can either make these antioxidants endogenously, or receive them through the diet.

BackgroundAs many studies revealed that oxidative stress due to the imbalance of reactive oxygen species (ROS) and antioxidant capacity is related with pathologic processes such as cardiovascular diseases, diabetes, as well as aging and obesity, the relationship between lifestyle and oxidative stress has recently gained much medical attention. However, little information exists on the effects of lifestyle on ROS in Korea. In this study, we investigated the effects of lifestyle on free oxygen radical levels in men and women in Korea.MethodsA total of 138 adults participated in this study from September 2007 to June 2010 at a health promotion center and department of family medicine. Information on the lifestyle of each participant was obtained by questionnaire. Biochemical markers and a free oxygen radical test (FORT) were also measured.ResultsThe average age was 47.28 ± 10.85 years and 79.7% were male. High sensitivity C-reactive protein (hs-CRP; r = 0.418, P = 0.012), triglycerides (r = -0.243, P = 0.008), hemoglobin (r = -0.445, P < 0.001), total protein (r = 0.210, P = 0.036), creatinine (r = -0.294, P = 0.001), fruit intake per day (P = 0.047), and smoking (P = 0.003) were related to the FORT levels in univariate analysis. Multiple linear regression analysis showed that hs-CRP (P = 0.039) was an independent predictor of serum FORT values. This statistical model can explain 78% of the variance in FORT values.ConclusionThis result suggests that hs-CRP showed a statistically significant positive association with FORT values. Further studies on the relationship between lifestyle and antioxidant capacity as well as ROS seem to be warranted to evaluate the overall effect of oxidative stress.