Current Pharmaceutical Design - Volume 24, Issue 40, 2018

Background: Cardiovascular diseases account for the highest mortality rate in the United States. The major underlying mechanism driving the onset and maintenance of cardiovascular diseases is atherosclerosis. Atherosclerosis is a chronic disease affecting large and medium-size arteries; it proceeds through four main stages along different decades of life, beginning at birth. Atherosclerosis is a consequence of oxidative stress, where homeostasis between endogenous antioxidants and reactive oxygen species is disrupted. Failure of intrinsic antioxidants and prophylactic antioxidant supplements to prevent atherosclerosis formation is an ongoing area of research in the race to avert, manage and cure atherosclerosis. Methods: The purpose of this work was to elucidate the actions of reactive oxygen species and oxidative stress on the formation of atherosclerosis as well as the different stages of atherosclerosis and the different mechanisms to prevent it. Through an extensive review of scientific literature, this paper correlates cell damage caused by oxidative stress to atheromatous plaque formation, as well as an in-depth analysis of high-density lipoproteins and enzymatic and non-enzymatic antioxidant role on atherosclerosis prevention. The antioxidant mechanism is overwhelmed by atherosclerotic processes and fails to be the ideal treatment of atherosclerosis. There is no scientific data that correlates prophylactic and non-prophylactic antioxidant treatment to a decrease in mortality or comorbidities pertaining to atherosclerosis. This is thought to be due to lack of consensus of optimal therapeutic doses, lack of reliable markers indicating which patient is to benefit from therapy and the chemical complexity of antioxidants in vivo. Current treatments for atherosclerosis include HMG-CoA reductase inhibitors which directly target low-density lipoproteins to tackle atherosclerotic plaque formation. Conclusion: HMG-CoA reductase inhibitors are not enough for the treatment of atherosclerosis given the complexity of the disease which has immune, musculoskeletal, genetic and hematologic aspects besides the involvement of lipids and lipoproteins. Therefore, other pharmacologic targets such as the PCSK9 enzyme and NFK- β should be researched in depth as possible treatments for atherosclerosis.

Background: Neurodegenerative diseases are becoming more and more common in today’s world. As people are continuously being exposed to exogenous factors like UV radiations, gamma rays, X-Rays, environmental pollutants and heavy metals, the cases of increased oxidative damage are increasing. Even though some amount of oxidative damage occurs in all metabolic reactions but their increase from the normal level in organisms causes neurodegenerative diseases. These neurodegenerative disorders like Alzeimers, Parkinsons disease and neuropsychiatric disorders such as schizophrenia, bipolar, depression are caused due to the decline in physiological and psychological functions caused by ROS and RNS. These ROS and RNS are formed as the result of excess oxidative damage in the system. Methods: The following article goes into detail explaining all the effects caused by excess oxidative damage like ROS/RNS formation and telomere shortening. Further, it explains the pathways of neurodegenerative diseases and neuropsychiatric diseases. This article also sheds light on the effective treatments of such disorders by changing lifestyle and activating antioxidant pathways. Conclusion: It is clear that neurodegenerative diseases are caused due to excess oxidative stress and alter the functioning of the central nervous system. The central nervous system undergoes neurodegenerative or neuropsychiatric changes.

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

Background: The eye is considered as a window of the disease, and a better understanding of neurodegenerative changes in the eye may help diagnose and manage neurodegenerative diseases including the diseases of brain, heart, kidney and liver. In the eye, the blood retinal barrier (BRB] is maintained by a combination of endothelial cells, pericytes, and glia. This BRB integrity is fundamental to the physiology of retinal cellular function and accurate vision. The role of endothelial dysfunction as a consequence of endothelial activation in the initiation and prolongation of neurovascular diseases of the retina is emerging. Methods: The observations made in this article are a result of our research over the years in the subject matter and also based on a literature search using PubMed with keywords including but not limited to endothelial, permeability, oxidative stress, ROS, TNF-α, retina, injury, and neurodegeneration. Several studies were identified that fulfilled the inclusion criteria. Overall, published studies support an association between endothelial activation, inflammation and oxidative stress in retinal diseases. Although the selection of specific endothelial activation biomarkers in the retina is less clear, there is an increased association between inflammation in the severity of diabetic retinopathy. Studies in other clinically relevant studies demonstrated a strong association of endothelial activation to alterations in mitochondrial respiratory chain complexes, pericyte integrity, microglial activation, neutrophil extracellular traps and elevated plasma concentrations of TNF-α. Conclusion: The compromise in BRB as a consequence of the neurovascular unit in the retinal tissue has gained a lot of attention and studies addressing these should result in a better understanding of the pathophysiology of retinal diseases. Although there are no specific retinal markers of endothelial activation and inflammation, future studies using specific models that display endothelial activation, inflammation and oxidative stress likely yield better understanding on the cause or effect relationship of endothelial activation in retinal diseases.

Background: Cell senescence constitutes a critical process to respond to a variety of insults and adverse circumstances. Senescence involves the detention of DNA replication and cell proliferation, and hence, genetic programs associated with DNA damage response, chromosome stability, chromatin rearrangement, epigenetic reprogramming, and cell cycle are tightly linked to the senescent phenotype. Although senescence increases with age, the real implication of senescence regulation in the progress of aging in humans is largely discussed. In this context, reactive oxygen species (ROS) accumulation has also been postulated to play a critical role in cell homeostasis, aging processes, and control of proliferation. Methods: The previous years have produced a high increase in data that refine our understanding of the role of ROS, and their relationship with epigenetic events, in determining cellular fate. Results: The accumulating evidence regarding the epigenetic regulation of ROS-mediated processes provides promising tools to deepen in our comprehension of the process of senescence, and to develop novel therapeutic strategies. In this review, we aim to provide an overview of the relationships between oxidative stress and cell senescence. Conclusion: We provide information about the role of epigenetic regulation in senescence and aging, collecting recent data from some examples of progeroid syndromes in which cell senescence, oxidative stress and epigenetic mechanisms are severely impaired. Finally, a collection of data is presented regarding current pharmacological approaches that either target or use oxidative stress-related factors or epigenetic regulators as strategies for disease treatment.

Background: Cancer is considered a major cause of death worldwide. The etiology of cancer is linked to environmental and genetic inheritance causes. Approximately 90 percent of all human cancers have an environmental cause (non-genetic inheritance) predominantly through lifestyle choices (smoking, diet, UV radiation) while the remaining due to infections and chemical exposure. Cancer is a multistage process that involves mutational changes and uncontrolled cell proliferation. Research has firmly established a causal and contributory role of oxidative stress and oxidative damage in cancer initiation and progression. Methods: The purpose of this article is to review the role that oxidative stress and reactive oxygen species play in the development of cancer. Both endogenous and exogenous sources of reactive oxygen species result in increased oxidative stress in the cell. Excess reactive oxygen fumed can result in damage to and modification of cellular macromolecules most importantly genomic DNA that can produce mutations. In addition, oxidative stress modulates gene expression of downstream targets involved in DNA repair, cell proliferation and antioxidants. The modulation of gene expression by oxidative stress occurs in part through activation or inhibition of transcription factors and second messengers. The role of single nuclear polymorphism for oxidative DNA repair and enzymatic antioxidants is important in determining the potential human cancer risk. Conclusion: oxidative stress and the resulting oxidative damage are important contributors to the formation and progression of cancer.

Background: Sulforaphane (SF, 1-isothiocyanato-4-(methyl-sulfinyl)-butane) is found in broccoli, cabbage and cauliflower. Methods: we performed a critical review on the antioxidative, chemopreventive and antitumor effects of SF from cruciferous vegetables against prostate cancers and molecular pathways. For a complete and reliable review, primary and secondary resources were used, including original and review articles, books and government documents published until March 2018. Articles that are in duplicity and disconnected are not considered for review. SF is derived from glucoraphanin (4-methyl-sulfinyl-butyl-glucosinate), being one of the most commonly found isothiocyanates in vegetables from Brassica spp., especially in broccoli samples. In vitro studies indicate that SF induces apoptosis in a dependent or non-dependent method of androgens by transcription of tumor suppressor genes, oxidation response and higher expression of phase II enzymes in prostate cancer cells. Sulforaphane also decreases transcription of the nuclear factor kB and antiapoptotic proteins, expression of cyclin D2 and survivin and DNA synthesis, increases Nrf2 gene activity, interferes with genome compacting by inhibition of histone deacetylases and disrupts Hsp90 complexes, which cause cell cycle arrest, mitosis interruption, activation of caspases and mitochondria depolarization. Conclusion: SF and cruciferous vegetables play antioxidative and chemopreventive role, delaying or blocking in vivo carcinogenesis, causing biochemical and epigenetic changes, preventing, delaying, or reversing preneoplastic or advanced prostate lesions, and frequently activating tumor cell death by intrinsic methods of apoptosis. These outcomes encourage the consumption of Brassica specimens, which could be easily achieved by the incorporation of food and vegetables rich in cruciferous isothiocyanates in the diet.

In this review we summarized some information regarding the link between kidney and oxidative stress. Accruing evidences indicated the kidney as a fundamental organ in reactive oxygen species (ROS) production. ROS are highly reactive and cause in single cells: protein alteration, DNA damage, cellular senescence and apoptosis; while the effect of ROS in biological tissues leads to a harmful oxidation effect on all their biochemical components: lipids, proteins, carbohydrates, and nucleic acids. Oxidative stress plays a role in the pathophysiology of renal impairment and is a mediator of CKD progression; furthermore, during substitutive therapy with haemodialysis or peritoneal dialysis and in case of transplantation, organism continues to be exposed to oxidation causing the development of major systemic comorbidities in particular cardiovascular diseases.

Background: In recent years, it has become more evident that oxidative stress is involved in the development of cardiovascular disease. Indeed, reactive oxygen species seems to be the common mechanism for endothelial dysfunction, vascular inflammation and arterial stiffness, resulting in a blood pressure increase and early vascular aging. Methods: This review presents the potential role of antioxidant nutrients and exercise for cardiovascular protection. Results: Flavonoids, vitamins and minerals present in some fruits and foliage are considered natural antioxidants. In fact, fruits and vegetables contain large amounts of antioxidants. Several clinical trials have extensively studied vitamin E, beta-carotene, vitamin C, polyphenols, plus selenium and zinc. In addition, many authors have been carried out clinical trials to evaluate the mechanisms of oxidative stress attenuation after exercise. Exercise responses may vary according to the Frequency, Intensity, Time and Type (FITT) principle, making it difficult to obtain a consensus concerning the exercise properties and redox status. High-intensity interval training (HIIT) has been reported as an efficient option for metabolic adaptations in a short time. Aerobic exercises must be performed at least three times a week, for two months or more, using moderate to vigorous intensity to promote a positive effect on oxidative stress and vascular function. Conclusion: The recognition of appropriate nutrients and exercise with antioxidant properties may be an important supportive approach to impair early vascular aging and to prevent cardiovascular disease.

Background: Oxidative stress (OxS) is a biochemical process characterized by an imbalance between the production of reactive species (RS) and antioxidants in favor of the former that subsequently induces the oxidative damage of biomolecules and alters cellular physiology. OxS exerts diverse effects and is associated with the pathophysiology of more than 100 diseases, as well as with the aging process. OxS also plays a role in maintaining the homeostasis of both animal and plant organisms. We analyze the role and mechanisms of the generation of RS and antioxidants both under physiological conditions and during aging and pathological processes. Likewise, the potential of antioxidant agents from the diet is considered, specifically fruits such as chayote. We focus on naringenin, a flavonoid with a high antioxidant capacity. Method: We conducted a literature review to present the state of the art of knowledge about the biological significance of oxidative stress and the effect of antioxidants in some edible fruits. Conclusions: Evidence supports the existence of RS, their physiological roles as well its harmful effects when oxidative stress occurs. In this sense, given the association of oxidative stress with diseases and aging the fruits rich in antioxidants are a feasible alternative to restore de redox balance if necessary.

Background: Oxygen is involved in a variety of physiological reactions in aerobic organisms, such as those produced in the electron transport chain, hydroxylation, and oxygenation. Reactive oxygen species (ROS) are naturally formed as byproducts from these previously reactions involving the O2 molecule; they are made up of superoxide anion (O2−), hydroxyl radical (HO−), hydrogen peroxide (H2O2), nitric oxide (NO), peroxyl (ROO−), and reactive aldehyde (ROCH). Under certain environmental stress conditions, ROS are accumulated causing cellular damage but also triggering the overexpression of several enzyme classes such as superoxide dismutases (SOD), catalases (CAT) and glutathione peroxidases (GPx), which represent an important intrinsic antioxidant defence line. Liver is a key organ in vertebrates including farm animals and human. The oxidative stress plays an important role in systemic malfunctions including hepatic, renal and immunological, disorders. Methods: This review presents a brief update about the relationship of oxidative stress with hepatic, renal and immunological malfunctions in stressed organisms. Cellular and exogenous hepatoprotective compounds share also the ability to scavenge ROS acting as antioxidants and in many cases as stimulators of immune response in stressed organisms. We present the effect of some hepatoprotectors on the hepatic, renal and immunological function in stressed mice by the jointed evaluation of biological and oxidative stress markers. Conclusion: Hepatoprotective effect of several exogenous compounds is very associated with their antioxidant capacity. This fact is relevant for keeping oxidant/antioxidant balance in the respective organs, but also for maintaining the physiological status of the whole organism.