scholarly journals Drug-Induced Oxidative Stress and Toxicity

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Damian G. Deavall ◽  
Elizabeth A. Martin ◽  
Judith M. Horner ◽  
Ruth Roberts
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Oxygen Radicals ◽  
Oxygen Species ◽  
Cardiac Damage ◽  
Drug Induced ◽  
Cellular Targets ◽  
Disease States ◽  
Normal Metabolism ◽  
Cellular Components

Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity.

scholarly journals Oxidative Stress and Autophagy in Cardiac Disease, Neurological Disorders, Aging and Cancer

2010 ◽  
Vol 3 (3) ◽  
pp. 168-177 ◽  
Author(s):  
Eric E. Essick ◽  
Flora Sam
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiac Disease ◽  
Neurological Disorders ◽  
Cell Stress ◽  
Nutrient Deprivation ◽  
Ros Production ◽  
Oxygen Species ◽  
Disease States ◽  
Cellular Components

Autophagy is a catalytic process of the bulk degradation of long-lived cellular components, ultimately resulting in lysosomal digestion within mature cytoplasmic compartments known as autophagolysosomes. Autophagy serves many functions in the cell, including maintaining cellular homeostasis, a means of cell survival during stress (e.g., nutrient deprivation or starvation) or conversely as a mechanism for cell death. Increased reactive oxygen species (ROS) production and the resulting oxidative cell stress that occurs in many disease states has been shown to induce autophagy. The following review focuses on the roles that autophagy plays in response to the ROS generated in several diseases.

scholarly journals The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species

2012 ◽  
Vol 23 (18) ◽  
pp. 3582-3590 ◽  
Author(s):  
Alawiah Alhebshi ◽  
Theodora C. Sideri ◽  
Sara L. Holland ◽  
Simon V. Avery
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Ribosomal Subunit ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Sulfur Protein ◽  
Iron Sulfur Protein ◽  
Cellular Components

Oxidative stress mediated by reactive oxygen species (ROS) is linked to degenerative conditions in humans and damage to an array of cellular components. However, it is unclear which molecular target(s) may be the primary “Achilles’ heel” of organisms, accounting for the inhibitory action of ROS. Rli1p (ABCE1) is an essential and highly conserved protein of eukaryotes and archaea that requires notoriously ROS-labile cofactors (Fe-S clusters) for its functions in protein synthesis. In this study, we tested the hypothesis that ROS toxicity is caused by Rli1p dysfunction. In addition to being essential, Rli1p activity (in nuclear ribosomal-subunit export) was shown to be impaired by mild oxidative stress in yeast. Furthermore, prooxidant resistance was decreased by RLI1 repression and increased by RLI1 overexpression. This Rlip1 dependency was abolished during anaerobicity and accentuated in cells expressing a FeS cluster–defective Rli1p construct. The protein's FeS clusters appeared ROS labile during in vitro incubations, but less so in vivo. Instead, it was primarily55FeS-cluster supply to Rli1p that was defective in prooxidant-exposed cells. The data indicate that, owing to its essential nature but dependency on ROS-labile FeS clusters, Rli1p function is a primary target of ROS action. Such insight could help inform new approaches for combating oxidative stress–related disease.

Oxidative stress and its implications in chronic kidney disease

2015 ◽  
Author(s):  
Nosratola D. Vaziri
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tissue Damage ◽  
Oxygen Radicals ◽  
Inflammatory Cells ◽  
Control Mechanisms ◽  
Oxygen Species ◽  
Low Levels

Reactive oxygen species (ROS) are produced at low levels physiologically and their production conveys signals and has specific functions. Control mechanisms ensure that this does not cause damage. ROS are highly reactive and cytotoxic and are also deliberately produced by inflammatory cells (granulocytes, macrophages) to kill pathogens. If these chemicals are released inappropriately or excessively, or if control mechanisms are under-functioning, bystander or unintended tissue damage may be caused. The concept of oxidative stress is based on the idea that in certain states, commonly inflammatory states, release of oxygen radicals may be excessive, or control mechanisms weakened, so that tissue damage occurs. In CKD, both overproduction and diminished control may apply. No effective therapies acting via these pathways have been established so far though there remain some candidates.

scholarly journals Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Hasna Tirichen ◽  
Hasnaa Yaigoub ◽  
Weiwei Xu ◽  
Changxin Wu ◽  
Rongshan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Cellular Reactive Oxygen Species ◽  
Kidney Disease Progression ◽  
Cellular Components

Mitochondria are known to generate approximately 90% of cellular reactive oxygen species (ROS). The imbalance between mitochondrial reactive oxygen species (mtROS) production and removal due to overproduction of ROS and/or decreased antioxidants defense activity results in oxidative stress (OS), which leads to oxidative damage that affects several cellular components such as lipids, DNA, and proteins. Since the kidney is a highly energetic organ, it is more vulnerable to damage caused by OS and thus its contribution to the development and progression of chronic kidney disease (CKD). This article aims to review the contribution of mtROS and OS to CKD progression and kidney function deterioration.

scholarly journals Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments

2019 ◽  
Vol 20 (18) ◽  
pp. 4472 ◽  
Author(s):  
Zuo ◽  
Prather ◽  
Stetskiv ◽  
Garrison ◽  
Meade ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
The Elderly ◽  
Chronic Obstructive ◽  
Oxygen Species ◽  
Novel Treatments ◽  
Disease States ◽  
Age Related

It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed in the elderly population. Inflammaging is associated with over-abundance of reactive oxygen species in the cell, which can lead to oxidation and damage of cellular components, increased inflammation, and activation of cell death pathways. This review focuses on inflammaging and its contribution to various age-related diseases such as cardiovascular disease, cancer, neurodegenerative diseases, chronic obstructive pulmonary disease, diabetes, and rheumatoid arthritis. Recently published mechanistic details of the roles of reactive oxygen species in inflammaging and various diseases will also be discussed. Advancements in potential treatments to ameliorate inflammaging, oxidative stress, and consequently, reduce the morbidity of multiple disease states will be explored.

scholarly journals Boosting the immune system with antioxidants: where are we now?

2019 ◽  
Vol 41 (1) ◽  
pp. 42-44 ◽  
Author(s):  
Luca Pangrazzi
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Immune System ◽  
System Performance ◽  
Oxygen Radicals ◽  
The Body ◽  
Oxygen Species ◽  
Immune Systems ◽  
Inflammatory Molecules ◽  
Fight Against Cancer

A strong immune system doesn't have to be just a dream. Over the last few decades, several strategies for boosting the immune system have been studied, with the aim of reducing the incidence and severity of infectious diseases. Furthermore, investigations into the possibility of improving the fight against cancer continue. Simple and powerful tools are already in our hands: the antioxidants. As we get older, or when we are particularly stressed, high levels of reactive oxygen species (ROS) accumulate, promoting oxidative stress and inflammation throughout the body. In this situation, normal body functions, in particular the immune systems, are severely impaired by an excess of oxygen radicals and pro-inflammatory molecules. For this reason, blocking the side effects of ROS with antioxidants may help us improve our immune system performance.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

Danshensu Rescues Ischemia/Reperfusion Caused Human Hepatocyte Death

2018 ◽  
Vol 17 (2) ◽  
pp. 117-121
Author(s):  
Sun Maw-Sheng ◽  
Liang Chun-Ya ◽  
Hsieh Po-Chun ◽  
Kuo Chan-Yen
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Oxygen Species ◽  
Good Strategy ◽  
Ros Accumulation ◽  
Dichlorofluorescin Diacetate ◽  
Hepatocyte Damage ◽  
Hepatocyte Death

Apoptosis of hepatocyte, under ischemia/reperfusion (IR) conditions, has been identified as an essential process in the progression of liver transplantation. Under these conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). Additionally, ROS overproduction may induce inflammation. As ROS accumulation appears to cause hepatocyte damage or death, there has been considerable interest in identifying the candidate natural products involved and in developing strategies to reduce oxidative stress. In this study, we use Danshensu as a candidate product to speculate whether has the protective effect on apoptotic hepatocyte upon IR. To speculate the apoptotic phenomena was reversed by Danshensu, we detected the p53, cleaved-caspase 3 expression by western blotting, as well as caspase-3 activity. Additionally, we analyzed the ROS levels by 2′,7′-dichlorofluorescin diacetate (DCF-DA) staining. We also detected the cell viability by WST-1. Results showed that Danshensu alleviated hypoxia-caused cell apoptosis via ROS overproduction. We suggested that Danshensu is a good strategy for treating hepatocyte damage upon IR.

scholarly journals 4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cytotoxic Effect ◽  
Neuroblastoma Cells ◽  
Reactive Oxygen ◽  
Prognostic Indicator ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

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