The role of ferroptosis in organ toxicity

2021 ◽  
pp. 096032712110529
Author(s):  
Fatemeh Yarmohammadi ◽  
A Wallace Hayes ◽  
Gholamreza Karimi
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Overload ◽  
Iron Chelators ◽  
Ros Generation ◽  
Oxygen Species ◽  
Organ Toxicity ◽  
Ros Accumulation ◽  
Dependent Form ◽  
Novel Therapeutic

Ferroptosis, an iron-dependent form of programmed cell death, is characterized by iron overload, increased reactive oxygen species (ROS) generation, and depletion of glutathione (GSH) and lipid peroxidation. Lipophilic antioxidants and iron chelators can prevent ferroptosis. GSH-dependent glutathione peroxidase 4 (GPX4) prevents lipid ROS accumulation. Ferroptosis is thought to be initiated through GPX4 inactivation. Moreover, mitochondrial iron overload derived from the degradation of ferritin is involved in increasing ROS generation. Ferroptosis has been suggested to explain the mechanism of action of organ toxicity induced by several drugs and chemicals. Inhibition of ferroptosis may provide novel therapeutic opportunities for treatment and even prevention of such organ toxicities.

scholarly journals A Novel Tetrapeptide Derivative Exhibits In Vitro Inhibition of Neutrophil-Derived Reactive Oxygen Species and Lysosomal Enzymes Release

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sumitra Miriyala ◽  
Manikandan Panchatcharam ◽  
Meera Ramanujam ◽  
Rengarajulu Puvanakrishnan
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Anion ◽  
Lysosomal Enzymes ◽  
Reactive Oxygen ◽  
Peptide Sequence ◽  
Ros Generation ◽  
Oxygen Species ◽  
Complement Factors

Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a tetrapeptide derivative PEP1261 (BOC-Lys(BOC)-Arg-Asp-Ser(tBu)-OtBU), a peptide sequence (39–42) of lactoferrin, studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation, lysosomal enzymes release, and enhanced expression of C proteins. The groundwork experimentation was concerned with the isolation of neutrophils from the normal and acute myocardial infarct rats to find out the efficacy of PEP1261 in the presence of a powerful neutrophil stimulant, phorbol 12-myristate 13 acetate (PMA). Stimulation of neutrophils with PMA resulted in an oxidative burst of superoxide anion and enhanced release of lysosomal enzymes and expression of complement proteins. The present study further demonstrated that the free radicals increase the complement factors in the neutrophils confirming the role of ROS. PEP1261 treatment significantly reduced the levels of superoxide anion and inhibited the release of lysosomal enzymes in the stimulated control and infarct rat neutrophils. This study demonstrated that PEP1261 significantly inhibited the effect on the ROS generation as well as the mRNA synthesis and expression of the complement factors in neutrophils isolated from infarct heart.

Flavonoids, the Family of Plant-derived Antioxidants making inroads into Novel Therapeutic Design against IR-induced Oxidative Stress in Parkinson’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Tapan Behl ◽  
Gagandeep Kaur ◽  
Aayush Sehgal ◽  
Gokhan Zengin ◽  
Sukhbir Singh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ionizing Radiation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Radiation Induced ◽  
Novel Therapeutic

Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various pieces of evidences assembled during preceding years reveal the pertinent role of ionizing radiation-induced oxidative stress in the progression of neurodegenerative insults such as Parkinson’s disease, which have been contributing to increased proliferation and generation of reactive oxygen species. Objective: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson’s disease and proposes novel therapeutic interventions of flavonoid family offering effective management and slowing down the progression of Parkinson’s disease. Method: Published papers were searched via MEDLINE, PubMed, etc. published to date for in-depth database collection. Results: The potential of oxidative damage may harm the non-targeted cells. It can also modulate the functions of central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerates the progression of Parkinson’s disease at the molecular, cellular, or tissue levels. In Parkinson’s disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. Conclusion: Rising interest has extensively engrossed on the clinical trial designs based on the plant derived family of antioxidants. They are known to exert multifarious impact either way in neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.

Extremely enhanced contaminant decomposition catalyzed by hemin via the coupling of persistent free radicals and ascorbic acid

2015 ◽  
Vol 51 (89) ◽  
pp. 16139-16142 ◽  
Author(s):  
Yuyuan Yao ◽  
Bin Jiang ◽  
Yajun Mao ◽  
Juan Chen ◽  
Zhenfu Huang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Ascorbic Acid ◽  
Free Radicals ◽  
Reactive Oxygen ◽  
Environmental Pollutant ◽  
Ros Generation ◽  
Oxygen Species ◽  
Positive Role ◽  
Rate Enhancement

A positive role of PFRs in enhancing reactive oxygen species (ROS) generation for an extreme rate enhancement in environmental pollutant decomposition is reported.

scholarly journals Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage

2015 ◽  
Vol 26 (18) ◽  
pp. 3150-3164 ◽  
Author(s):  
Gaurav N. Joshi ◽  
Alexandra M. Goetjen ◽  
David A. Knecht
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Lung Fibrosis ◽  
Membrane Damage ◽  
Cell Types ◽  
Silica Particles ◽  
Ros Generation ◽  
Oxygen Species ◽  
Latex Particles

Chronic inhalation of silica particles causes lung fibrosis and silicosis. Silica taken up by alveolar macrophages causes phagolysosomal membrane damage and leakage of lysosomal material into the cytoplasm to initiate apoptosis. We investigated the role of reactive oxygen species (ROS) in this membrane damage by studying the spatiotemporal generation of ROS. In macrophages, ROS generated by NADPH oxidase 2 (NOX2) was detected in phagolysosomes containing either silica particles or nontoxic latex particles. ROS was only detected in the cytoplasm of cells treated with silica and appeared in parallel with an increase in phagosomal ROS, as well as several hours later associated with mitochondrial production of ROS late in apoptosis. Pharmacological inhibition of NOX activity did not prevent silica-induced phagolysosomal leakage but delayed it. In Cos7 cells, which do not express NOX2, ROS was detected in silica-containing phagolysosomes that leaked. ROS was not detected in phagolysosomes containing latex particles. Leakage of silica-containing phagolysosomes in both cell types was transient, and after resealing of the membrane, endolysosomal fusion continued. These results demonstrate that silica particles can generate phagosomal ROS independent of NOX activity, and we propose that this silica-generated ROS can cause phagolysosomal leakage to initiate apoptosis.

scholarly journals Novel Approach to Reactive Oxygen Species in Nontransfusion-Dependent Thalassemia

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Paul I. Tyan ◽  
Amr H. Radwan ◽  
Assaad Eid ◽  
Anthony G. Haddad ◽  
David Wehbe ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Overload ◽  
Cell Injury ◽  
Clinical Manifestations ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Ineffective Erythropoiesis ◽  
Chronic Anemia ◽  
Globin Chains

The term Nontransfusion dependent thalassaemia (NTDT) was suggested to describe patients who had clinical manifestations that are too severe to be termed minor yet too mild to be termed major. Those patients are not entirely dependent on transfusions for survival. If left untreated, three main factors are responsible for the clinical sequelae of NTDT: ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. Reactive oxygen species (ROS) generation in NTDT patients is caused by 2 major mechanisms. The first one is chronic hypoxia resulting from chronic anemia and ineffective erythropoiesis leading to mitochondrial damage and the second is iron overload also due to chronic anemia and tissue hypoxia leading to increase intestinal iron absorption in thalassemic patients. Oxidative damage by reactive oxygen species (generated by free globin chains and labile plasma iron) is believed to be one of the main contributors to cell injury, tissue damage, and hypercoagulability in patients with thalassemia. Independently increased ROS has been linked to a myriad of pathological outcomes such as leg ulcers, decreased wound healing, pulmonary hypertension, silent brain infarcts, and increased thrombosis to count a few. Interestingly many of those complications overlap with those found in NTDT patients.

In the idiopathic inflammatory myopathies (IIM), do reactive oxygen species (ROS) contribute to muscle weakness?

2015 ◽  
Vol 74 (7) ◽  
pp. 1340-1346 ◽  
Author(s):  
Adam P Lightfoot ◽  
Anne McArdle ◽  
Malcolm J Jackson ◽  
Robert G Cooper
Keyword(s):  
Reactive Oxygen Species ◽  
Muscle Weakness ◽  
Inflammatory Cell ◽  
Immune Cell ◽  
Ros Generation ◽  
Muscle Dysfunction ◽  
Idiopathic Inflammatory Myopathies ◽  
Oxygen Species ◽  
Inflammatory Myopathies

The idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune disorders, collectively known as myositis. Affected patients present with proximal muscle weakness, which usually improves following treatment with immunosuppressants, but often incompletely so, thus many patients remain weak. IIMs are characterised histologically by inflammatory cell infiltrates into skeletal muscle and overexpression of major histocompatibility complex I on muscle cell surfaces. Although inflammatory cell infiltrates represent a major feature of myositis there is growing evidence that muscle weakness correlates only poorly with the degree of cellular infiltration, while weakness may in fact precede such infiltrations. The mechanisms underpinning such non-immune cell mediated weakness in IIM are poorly understood. Activation of the endoplasmic reticulum stress pathways appears to be a potential contributor. Data from non-muscle cells indicate that endoplasmic reticulum stress results in altered redox homeostasis capable of causing oxidative damage. In myopathological situations other than IIM, as seen in ageing and sepsis, evidence supports an important role for reactive oxygen species (ROS). Modified ROS generation is associated with mitochondrial dysfunction, depressed force generation and activation of muscle catabolic and autophagy pathways. Despite the growing evidence demonstrating a key role for ROS in skeletal muscle dysfunction in myopathologies other than IIM, no research has yet investigated the role of modified generation of ROS in inducing the weakness characteristic of IIM. This article reviews current knowledge regarding muscle weakness in the absence of immune cells in IIM, and provides a background to the potential role of modified ROS generation as a mechanism of muscle dysfunction. The authors suggest that ROS-mediated mechanisms are potentially involved in non-immune cell mediated weakness seen in IIM and outline how these mechanisms might be investigated in this context. This appears a timely strategy, given recent developments in targeted therapies which specifically modify ROS generation.

scholarly journals Cross talk between increased intracellular zinc (Zn2+) and accumulation of reactive oxygen species in chemical ischemia

2017 ◽  
Vol 313 (4) ◽  
pp. C448-C459 ◽  
Author(s):  
Kira G. Slepchenko ◽  
Qiping Lu ◽  
Yang V. Li
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Cross Talk ◽  
Reactive Oxygen ◽  
Glucose Deprivation ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Ros Accumulation ◽  
Ischemic Stress

Both zinc (Zn2+) and reactive oxygen species (ROS) have been shown to accumulate during hypoxic-ischemic stress and play important roles in pathological processes. To understand the cross talk between the two of them, here we studied Zn2+ and ROS accumulation by employing fluorescent probes in HeLa cells to further the understanding of the cause and effect relationship of these two important cellular signaling systems during chemical-ischemia, stimulated by oxygen and glucose deprivation (OGD). We observed two Zn2+ rises that were divided into four phases in the course of 30 min of OGD. The first Zn2+ rise was a transient, which was followed by a latent phase during which Zn2+ levels recovered; however, levels remained above a basal level in most cells. The final phase was the second Zn2+ rise, which reached a sustained plateau called Zn2+ overload. Zn2+ rises were not observed when Zn2+ was removed by TPEN (a Zn2+ chelator) or thapsigargin (depleting Zn2+ from intracellular stores) treatment, indicating that Zn2+ was from intracellular storage. Damaging mitochondria with FCCP significantly reduced the second Zn2+ rise, indicating that the mitochondrial Zn2+ accumulation contributes to Zn2+ overload. We also detected two OGD-induced ROS rises. Two Zn2+ rises preceded two ROS rises. Removal of Zn2+ reduced or delayed OGD- and FCCP-induced ROS generation, indicating that Zn2+ contributes to mitochondrial ROS generation. There was a Zn2+-induced increase in the functional component of NADPH oxidase, p47phox, thus suggesting that NADPH oxidase may mediate Zn2+-induced ROS accumulation. We suggest a new mechanism of cross talk between Zn2+ and mitochondrial ROS through positive feedback processes that eventually causes excessive free Zn2+ and ROS accumulations during the course of ischemic stress.

scholarly journals Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3769
Author(s):  
Katerina Hadrava Hadrava Vanova ◽  
Chunzhang Yang ◽  
Leah Meuter ◽  
Jiri Neuzil ◽  
Karel Pacak
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Cells ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Promising Therapeutic Target ◽  
Ros Accumulation ◽  
Intracellular Ros

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors derived from neural crest cells. Germline variants in approximately 20 PHEO/PGL susceptibility genes are found in about 40% of patients, half of which are found in the genes that encode succinate dehydrogenase (SDH). Patients with SDH subunit B (SDHB)-mutated PHEO/PGL exhibit a higher likelihood of developing metastatic disease, which can be partially explained by the metabolic cell reprogramming and redox imbalance caused by the mutation. Reactive oxygen species (ROS) are highly reactive molecules involved in a multitude of important signaling pathways. A moderate level of ROS production can help regulate cellular physiology; however, an excessive level of oxidative stress can lead to tumorigenic processes including stimulation of growth factor-dependent pathways and the induction of genetic instability. Tumor cells effectively exploit antioxidant enzymes in order to protect themselves against harmful intracellular ROS accumulation, which highlights the essential balance between ROS production and scavenging. Exploiting ROS accumulation can be used as a possible therapeutic strategy in ROS-scavenging tumor cells. Here, we focus on the role of ROS production in PHEO and PGL, predominantly in SDHB-mutated cases. We discuss potential strategies and approaches to anticancer therapies by enhancing ROS production in these difficult-to-treat tumors.

scholarly journals Every Coin Has Two Sides: Reactive Oxygen Species during Rice–Magnaporthe oryzae Interaction

2019 ◽  
Vol 20 (5) ◽  
pp. 1191 ◽  
Author(s):  
Yanjun Kou ◽  
Jiehua Qiu ◽  
Zeng Tao
Keyword(s):  
Reactive Oxygen Species ◽  
Magnaporthe Oryzae ◽  
Rice Blast ◽  
Blast Resistance ◽  
Reactive Oxygen ◽  
Redox Balance ◽  
Ros Generation ◽  
Oxygen Species ◽  
Rice Blast Resistance ◽  
Ros Accumulation

Reactive oxygen species (ROS) are involved in many important processes, including the growth, development, and responses to the environments, in rice (Oryza sativa) and Magnaporthe oryzae. Although ROS are known to be critical components in rice–M. oryzae interactions, their regulations and pathways have not yet been completely revealed. Recent studies have provided fascinating insights into the intricate physiological redox balance in rice–M. oryzae interactions. In M. oryzae, ROS accumulation is required for the appressorium formation and penetration. However, once inside the rice cells, M. oryzae must scavenge the host-derived ROS to spread invasive hyphae. On the other side, ROS play key roles in rice against M. oryzae. It has been known that, upon perception of M. oryzae, rice plants modulate their activities of ROS generating and scavenging enzymes, mainly on NADPH oxidase OsRbohB, by different signaling pathways to accumulate ROS against rice blast. By contrast, the M. oryzae virulent strains are capable of suppressing ROS accumulation and attenuating rice blast resistance by the secretion of effectors, such as AvrPii and AvrPiz-t. These results suggest that ROS generation and scavenging of ROS are tightly controlled by different pathways in both M. oryzae and rice during rice blast. In this review, the most recent advances in the understanding of the regulatory mechanisms of ROS accumulation and signaling during rice–M. oryzae interaction are summarized.

scholarly journals Reactive Oxygen Species (Ros-Induced) Ros Release

2000 ◽  
Vol 192 (7) ◽  
pp. 1001-1014 ◽  
Author(s):  
Dmitry B. Zorov ◽  
Charles R. Filburn ◽  
Lars-Oliver Klotz ◽  
Jay L. Zweier ◽  
Steven J. Sollott
Keyword(s):  
Reactive Oxygen Species ◽  
Cardiac Myocytes ◽  
Cell Biology ◽  
Mitochondrial Permeability Transition ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Mitochondrial Ros ◽  
Ros Accumulation

We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of tetramethylrhodamine derivatives, which also served to report the mitochondrial transmembrane potential, ΔΨ. This ROS accumulation reproducibly triggered abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b) mitochondria became permeable for calcein (∼620 daltons) concurrently with depolarization. These photodynamically produced “triggering” ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time required for triggering ROS to induce the MPT was dependent on intrinsic cellular ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused by triggering ROS coincided with a burst of mitochondrial ROS generation, as measured by dichlorofluorescein fluorescence, which we have termed mitochondrial “ROS-induced ROS release” (RIRR). This MPT induction/RIRR phenomenon in cardiac myocytes often occurred synchronously and reversibly among long chains of adjacent mitochondria demonstrating apparent cooperativity. The observed link between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell biology.

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