Doxorubicin-Induced In Vivo Nephrotoxicity Involves Oxidative Stress- Mediated Multiple Pro- and Anti-Apoptotic Signaling Pathways

2012 ◽  
Vol 9 (4) ◽  
pp. 282-295 ◽  
Author(s):  
Tejas S. Lahoti ◽  
Darshan Patel ◽  
Venkatesh Thekkemadom ◽  
Robert Beckett ◽  
Sidhartha D. Ray
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Apoptotic Signaling

scholarly journals Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lingyu Yang ◽  
Dehai Xian ◽  
Xia Xiong ◽  
Rui Lai ◽  
Jing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Cost ◽  
Natural Agents ◽  
Molecular Damage ◽  
And Control

Proanthocyanidins (PCs) are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerousin vitroandin vivostudies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, anti-inflammation, immunomodulation, DNA repair, and antitumor activity. Accumulation of prooxidants such as reactive oxygen species (ROS) exceeding cellular antioxidant capacity results in oxidative stress (OS), which can damage macromolecules (DNA, lipids, and proteins), organelles (membranes and mitochondria), and whole tissues. OS is implicated in the pathogenesis and exacerbation of many cardiovascular, neurodegenerative, dermatological, and metabolic diseases, both through direct molecular damage and secondary activation of stress-associated signaling pathways. PCs are promising natural agents to safely prevent acute damage and control chronic diseases at relatively low cost. In this review, we summarize the molecules and signaling pathways involved in OS and the corresponding therapeutic mechanisms of PCs.

scholarly journals Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Pan ◽  
Lin Zheng ◽  
Jiawei Fang ◽  
Ye Lin ◽  
Hehuan Lai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Signaling Pathways ◽  
Bone Microarchitecture ◽  
Reactive Oxygen ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species

Osteoporosis is characterized by a decrease in bone mass and destruction of the bone microarchitecture, and it commonly occurs in postmenopausal women and the elderly. Overactivation of osteoclasts caused by the inflammatory response or oxidative stress leads to osteoporosis. An increasing number of studies have suggested that intracellular reactive oxygen species (ROS) are strongly associated with osteoclastogenesis. As a novel angiotensin (Ang) II receptor blocker (ARB), azilsartan was reported to be associated with the inhibition of intracellular oxidative stress processes. However, the relationship between azilsartan and osteoclastogenesis is still unknown. In this study, we explored the effect of azilsartan on ovariectomy-induced osteoporosis in mice. Azilsartan significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and downregulated the expression of osteoclast-associated markers (Nfatc1, c-Fos, and Ctsk) in vitro. Furthermore, azilsartan reduced RANKL-induced ROS production by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Mechanistically, azilsartan inhibited the activation of MAPK/NF-κB signaling pathways, while Nrf2 silencing reversed the inhibitory effect of azilsartan on MAPK/NF-κB signaling pathways. Consistent with the in vitro data, azilsartan administration ameliorated ovariectomy (OVX)-induced osteoporosis, and decreased ROS levels in vivo. In conclusion, azilsartan inhibited oxidative stress and may be a novel treatment strategy for osteoporosis caused by osteoclast overactivation.

Abstract 1599: Hydrogen Sulfide Mediates Myocardial Preconditioning via Upregulation of Antioxidant and Anti-Apoptotic Signaling Pathways

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
John W Calvert ◽  
Saurabh Jha ◽  
Susheel Gundewar ◽  
Mark R Duranski ◽  
David J Lefer
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Nuclear Localization ◽  
Troponin I ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Apoptotic Signaling ◽  
Cellular Targets ◽  
Myocardial Preconditioning

The emergence of hydrogen sulfide (H 2 S) as a potent cardioprotective mediator necessitates the elucidation of its cytoprotective mechanisms. Therefore, we evaluated potential mechanisms of H 2 S-mediated cardioprotection using an in vivo model of preconditioning (PC). The H 2 S donor, IK1001 (100 μg/kg), or vehicle was administered to mice via an intravenous injection 24 hours prior to left coronary artery occlusion and reperfusion. Mice were subjected to 45 min of myocardial ischemia followed by reperfusion for up to 24 hr, during which time the extent of myocardial infarction was evaluated, serum troponin-I levels were measured, and the degree of oxidative stress was assessed. In separate studies, mice were treated with IK1001 and myocardial tissue was collected during both the early (30 min and 2hr) and late (24 hr) PC periods to evaluate potential cellular targets of H 2 S. IK1001 provided profound protection against ischemic injury as evidenced by significant decreases in infarct size, serum troponin-I levels, and oxidative stress. Additional studies revealed that during the early PC period H 2 S increased the nuclear localization of Nrf-2, a transcription factor that regulates the gene expression of a number of antioxidants, and increased the nuclear localization of phosphorylated STAT-3. During the late PC period, H 2 S increased the expression of the antioxidants, Trx-1 and Trx-2, increased the expression of HSP90, HSP70, Bcl-2, and Bcl-xL and also inactivated the pro-apoptogen Bad. Our results reveal that the cardioprotective effects of H 2 S are mediated in large part by a combination of antioxidant and anti-apoptotic signaling.

scholarly journals The apelin-13 peptide protects the heart against apoptosis through the ERK/MAPK and PI3K/AKT signaling pathways.

2020 ◽  
Author(s):  
Xuejun Wang ◽  
Li Zhang ◽  
Mengwen Feng ◽  
Hao Zhang ◽  
Jia Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Signaling Pathways ◽  
Akt Signaling ◽  
Blue Staining ◽  
Endocrine Activity ◽  
Multiple Systems ◽  
Erk Mapk

Abstract Background: It has been acknowledged that endocrine activity is associated with the function of multiple systems in vivo. The apelin-13 peptide has been demonstrated to play a crucial role in various physiological and pathological processes. However, whether apelin-13 peptide function in DOX induced cardiotoxicity is unknown. Methods: We explored the function and mechanism of the apelin-13 peptide in apoptosis and oxidative stress by CCK-8, trypan blue staining, TUNEL, LDH, JC-1 and western blot in vitro. Then we verified the effect of apelin-13 in vivo by serum CKMB and LDH, echocardiography, sirius red staining and HE staining assay.Results: Treatment with the apelin-13 peptide significantly enhanced cell viability, mitochondrial membrane potential, and reduced LDH release, rate of apoptosis and activation of caspase-3 in vitro. In mice, the apelin-13 peptide alleviated the heart failure induced by DOX treatment. ML-221 inhibited the activation of ERK, PI3K and AKT proteins phosphorylation by apelin-13.Conclusion: The apelin-13 and APJ interaction on the cell membrane inhibits apoptosis though the ERK/MAPK and PI3K/AKT signaling pathways. The application of apelin-13 may be a novel therapeutic strategy in oxidative stress-induced heart failure therapy.

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