scholarly journals Regression Modeling of the Antioxidant-to-Nephroprotective Relation Shows the Pivotal Role of Oxidative Stress in Cisplatin Nephrotoxicity

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1355
Author(s):  
Alfredo G. Casanova ◽  
Mykola Harvat ◽  
Laura Vicente-Vicente ◽  
Óscar J. Pellicer-Valero ◽  
Ana I. Morales ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Utility ◽  
Antioxidant Effect ◽  
Tubular Dysfunction ◽  
Antioxidant Treatment ◽  
Cisplatin Nephrotoxicity ◽  
Relative Contribution ◽  
Glomerular Filtration Rate Decline ◽  
Two Parameters

The clinical utility of the chemotherapeutic drug cisplatin is significantly limited by its nephrotoxicity, which is characterized by electrolytic disorders, glomerular filtration rate decline, and azotemia. These alterations are consequences of a primary tubulopathy causing injury to proximal and distal epithelial cells, and thus tubular dysfunction. Oxidative stress plays a role in cisplatin nephrotoxicity and cytotoxicity, but its relative contribution to overall toxicity remains unknown. We studied the relation between the degree of oxidative reduction (provided by antioxidant treatment) and the extent of nephrotoxicity amelioration (i.e., nephroprotection) by means of a regression analysis of studies in animal models. Our results indicate that a linear relation exists between these two parameters, and that this relation very nearly crosses the value of maximal nephroprotection at maximal antioxidant effect, suggesting that oxidative stress seems to be a pivotal and mandatory mechanism of cisplatin nephrotoxicity, and, hence, an interesting, rationale-based target for clinical use. Our model also serves to identify antioxidants with enhanced effectiveness by comparing their actual nephroprotective power with that predicted by their antioxidant effect. Among those, this study identified nanoceria, erythropoietin, and maltol as highly effective candidates affording more nephroprotection than expected from their antioxidant effect for prospective clinical development.

scholarly journals Cytoprotection of human endothelial cells from oxidative stress by polyphenols: the role of gene expression versus direct antioxidant effect

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Xinyu Wang ◽  
James Bynum ◽  
Salomon Stavchansky ◽  
Michael Dubick ◽  
Robert Hackman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Endothelial Cells ◽  
Antioxidant Effect ◽  
Human Endothelial Cells

scholarly journals The Role of Traditional Chinese Medicine in the Regulation of Oxidative Stress in Treating Coronary Heart Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Xinyu Yang ◽  
Tianmai He ◽  
Songjie Han ◽  
Xiaoyu Zhang ◽  
Yang Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Antioxidant Treatment ◽  
Molecular Systems ◽  
Artery Disease ◽  
Signal Activation

Oxidative stress has been closely related with coronary artery disease. In coronary heart disease (CHD), an excess of reactive oxygen species (ROS) production generates endothelial cell and smooth muscle functional disorders, leading to a disequilibrium between the antioxidant capacity and prooxidants. ROS also leads to inflammatory signal activation and mitochondria-mediated apoptosis, which can promote and increase the occurrence and development of CHD. There are several kinds of antioxidative and small molecular systems of antioxidants, such as β-carotene, ascorbic acid, α-tocopherol, and reduced glutathione (GSH). Studies have shown that antioxidant treatment was effective and decreased the risk of CHD, but the effect of the treatment varies greatly. Traditional Chinese medicine (TCM) has been utilized for thousands of years in China and is becoming increasingly popular all over the world, especially for the treatments of cardiovascular diseases. This review will concentrate on the evidence of the action mechanism of TCM in preventing CHD by modulating oxidative stress-related signaling pathways.

scholarly journals The Role of Antioxidants in the Management of Obsessive-Compulsive Disorder

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Fatemeh Baratzadeh ◽  
Sepideh Elyasi ◽  
Amir Hooshang Mohammadpour ◽  
Sofia Salari ◽  
Amirhossein Sahebkar
Keyword(s):  
Oxidative Stress ◽  
Obsessive Compulsive Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Human Studies ◽  
Large Sample Size ◽  
Antioxidant Treatment ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder that has a significant effect on the quality of life. The most effective treatment for OCD is the combination of selective serotonin reuptake inhibitors (SSRI) with cognitive behavior therapy (CBT). However, several adverse effects have been linked with this usual pharmacotherapy, and it is unsuccessful in many patients. The exact pathophysiology of OCD is not completely known, though the role of oxidative stress in its pathogenesis has been proposed recently. This review presents an overview of animal and human studies of antioxidant treatment for OCD. The use of antioxidants against oxidative stress is a novel treatment for several neurodegenerative and neuropsychiatric disorders. Among antioxidants, NAC was one of the most studied drugs on OCD, and it showed a significant improvement in OCD symptoms. Thus, antioxidants could be promising as an adjuvant treatment for OCD. However, a limited number of human studies are conducted on these agents, and for better judgment, human studies with a large sample size are necessary.

Antioxidant Treatment Reverses Organ Failure in Rat Model of Sepsis: Role of Antioxidant Enzymes Imbalance, Neutrophil Infiltration, and Oxidative Stress

2011 ◽  
Vol 167 (2) ◽  
pp. e307-e313 ◽  
Author(s):  
Michael Andrades ◽  
Cristiane Ritter ◽  
Marcos Roberto de Oliveira ◽  
Emílio L. Streck ◽  
José Cláudio Fonseca Moreira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Organ Failure ◽  
Rat Model ◽  
Neutrophil Infiltration ◽  
Antioxidant Treatment ◽  
And Oxidative Stress

scholarly journals A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mi Liu ◽  
Zhanjun Jia ◽  
Ying Sun ◽  
Aihua Zhang ◽  
Tianxin Yang
Keyword(s):  
Oxidative Stress ◽  
Renal Dysfunction ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Apoptotic Response ◽  
Cisplatin Nephrotoxicity ◽  
Histological Damage ◽  
Structural Injury ◽  
Elevated Blood Urea Nitrogen

Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN) and histological damage. Consistently, these mice also showed increased proinflammatory cytokines such as TNF-α, IL-6, and IL-1βin circulation and/or kidney tissues. Meanwhile, circulating thiobarbituric aid-reactive substances (TBARS) and renal apoptotic indices including caspase-3, Bak, and Bax were all elevated. However, application of GYY4137 further aggravated renal dysfunction and kidney structural injury in line with promoted inflammation, oxidative stress, and apoptotic response following cisplatin treatment. Taken together, our results suggested that GYY4137 exacerbated cisplatin-induced nephrotoxicity in mice possibly through promoting inflammation, oxidative stress, and apoptotic response.

scholarly journals DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy

2021 ◽  
Vol 22 (11) ◽  
pp. 5675
Author(s):  
Jinglong Chen ◽  
Danping Wang ◽  
Yibo Zong ◽  
Xiaojing Yang
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunction ◽  
Liver Diseases ◽  
Antioxidant Effect ◽  
Cellular Damage ◽  
Autophagic Flux

Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H2O2-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H2O2 and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl4 and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy.

scholarly journals Antioxidant treatment attenuates lactate production in diabetic nephropathy

2017 ◽  
Vol 312 (1) ◽  
pp. F192-F199 ◽  
Author(s):  
Christoffer Laustsen ◽  
Per Mose Nielsen ◽  
Thomas Stokholm Nørlinger ◽  
Haiyun Qi ◽  
Uffe Kjærgaard Pedersen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Krebs Cycle ◽  
Lactate Production ◽  
Polyol Pathway ◽  
Antioxidant Treatment ◽  
Early Diabetes ◽  
Lactate Dehydrogenase Activity ◽  
Metabolic Alterations

The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) via the drinking water. Examinations were performed 2, 3, and 4 wk after the induction of diabetes by using a 3T Clinical MR system equipped with a dual tuned 13C/1H-volume rat coil. The rats received intravenous hyperpolarized [1-13C]pyruvate and were imaged using a slice-selective 13C-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels, indicating an intact glucose-alanine cycle, or [13C]bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress in renal metabolic alterations occurring in early diabetes.

The controversial role of vitamin D as an antioxidant: results from randomised controlled trials

2018 ◽  
Vol 32 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Sara Tagliaferri ◽  
Debora Porri ◽  
Rachele De Giuseppe ◽  
Matteo Manuelli ◽  
Francesco Alessio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Vitamin D Supplementation ◽  
Antioxidant Effect ◽  
Present Review ◽  
Extensive Literature ◽  
Oxidative Stress Biomarkers ◽  
Skeletal Tissue ◽  
Randomised Controlled

AbstractIncreased oxidative stress has been implicated as a potential causal factor in the development of several diseases. In the last decade, an extensive literature has been produced on vitamin D, not limited to its well-known function like a steroid hormone on skeletal tissue, but for its potential pleiotropic role in human health. Several researchers have suggested relationships between vitamin D intake and health outcomes such as cancer prevention and increased immunity, or possible role in preventing diabetes, and in inflammation. Little is known about its antioxidant effect. The aim of the present review was to explore major evidence regarding the potential scavenger capacity of vitamin D in high-evidence human studies. Studies considered by the present review suggest that the potential role of vitamin D as an antioxidant could not be confirmed. Current literature showed controversial effects about the ability of cholecalciferol to prevent or ameliorate oxidative stress biomarkers, and there is need of further and high-quality studies testing the antioxidant effect of vitamin D supplementation.

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