Mechanisms of cisplatin ototoxicity: theoretical review

2013 ◽  
Vol 127 (6) ◽  
pp. 536-541 ◽  
Author(s):  
M S Gonçalves ◽  
A F Silveira ◽  
A R Teixeira ◽  
M A Hyppolito
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Chemotherapeutic Agent ◽  
Apoptotic Cell ◽  
Experimental Studies ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Receptor Potential ◽  
Oxygen Species ◽  
Malignant Tumours

AbstractIntroduction:Cisplatin is an effective chemotherapeutic agent commonly used in the treatment of malignant tumours, but ototoxicity is a significant side effect.Objectives:To discuss the mechanisms of cisplatin ototoxicity and subsequent cell death, and to present the results of experimental studies.Material and methods:We conducted a systematic search for data published in national and international journals and books, using the Medline, SciELO, Bireme, LILACS and PubMed databases.Results:The nicotinamide adenine dinucleotide phosphate oxidase 3 isoform (also termed NOX3) seems to be the main source of reactive oxygen species in the cochlea. These reactive oxygen species react with other molecules and trigger processes such as lipid peroxidation of the plasma membrane and increases in expression of the transient vanilloid receptor potential 1 ion channel.Conclusion:Cisplatin ototoxicity proceeds via the formation of reactive oxygen species in cochlear tissue, with apoptotic cell death as a consequence.

scholarly journals Doxorubicin-Induced Fetal Mesangial Cell Death Occurs Independently of TRPC6 Channel Upregulation but Involves Mitochondrial Generation of Reactive Oxygen Species

2021 ◽  
Vol 22 (14) ◽  
pp. 7589
Author(s):  
Anberitha T. Matthews ◽  
Hitesh Soni ◽  
Katherine E. Robinson-Freeman ◽  
Theresa A. John ◽  
Randal K. Buddington ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Transient Receptor Potential ◽  
Mesangial Cell ◽  
Reactive Oxygen ◽  
Receptor Potential ◽  
Oxygen Species ◽  
Glomerular Mesangial Cell ◽  
Trpc6 Channel ◽  
Fetal Pig

Doxorubicin (DOX), a category D pregnancy drug, is a chemotherapeutic agent that has been shown in animal studies to induce fetal toxicity, including renal abnormalities. Upregulation of the transient receptor potential cation (TRPC) 6 channel is involved in DOX-induced podocyte apoptosis. We have previously reported that TRPC6-mediated Ca2+ signaling promotes neonatal glomerular mesangial cell (GMC) death. However, it is unknown whether DOX alters mesangial TRPC expression or viability in the fetus. In this study, cell growth was tracked in control and DOX-treated primary GMCs derived from fetal pigs. Live-cell imaging demonstrated that exposure to DOX inhibited the proliferation of fetal pig GMCs and induced cell death. DOX did not alter the TRPC3 expression levels. By contrast, TRPC6 protein expression in the cells was markedly reduced by DOX. DOX treatment also attenuated the TRPC6-mediated intracellular Ca2+ elevation. DOX stimulated mitochondrial reactive oxygen species (mtROS) generation and mitophagy by the GMCs. The DOX-induced mtROS generation and apoptosis were reversed by the mitochondria-targeted antioxidant mitoquinone. These data suggest that DOX-induced fetal pig GMC apoptosis is independent of TRPC6 channel upregulation but requires mtROS production. The mtROS-dependent GMC death may contribute to DOX-induced fetal nephrotoxicity when administered prenatally.

Reactive Oxygen Species (ROS): Key components in Cancer Therapies

2021 ◽  
Vol 21 ◽  
Author(s):  
Biswa Mohan Sahoo ◽  
Bimal Krishna Banik ◽  
Preetismita Borah ◽  
Adya Jain
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Hypochlorous Acid ◽  
Molecular Form ◽  
Experimental Studies ◽  
Reactive Oxygen ◽  
Chemotherapeutic Agents ◽  
Cancer Therapies ◽  
Oxygen Species ◽  
Cell Organelles

: Reactive oxygen species (ROS) refer to the highly reactive substances, which contain oxygen radicals. Hypochlorous acid, peroxides, superoxide, singlet oxygen, alpha-oxygen and hydroxyl radicals are the major examples of ROS. Generally, the reduction of oxygen (O2) in molecular form produces superoxide (•O2−) anion. ROS are produced during a variety of biochemical reactions within the cell organelles, such as endoplasmic reticulum, mitochondria and peroxisome. Naturally, ROS are also formed as a byproduct of the normal metabolism of oxygen. The production of ROS can be induced by various factors such as heavy metals, tobacco, smoke, drugs, xenobiotics, pollutants and radiation. From various experimental studies, it is reported that ROS act as either tumor suppressing or tumor promoting agent. The elevated levels of ROS can arrest the growth of tumor through the persistent increase in cell cycle inhibition. The increased level of ROS can induce apoptosis by both intrinsic and extrinsic pathways. ROS are considered to be tumor suppressing agent as the production of ROS is due to the use of most of the chemotherapeutic agents in order to activate the cell death. The cytotoxic effect of ROS provides impetus towards apoptosis, but in higher levels, ROS can cause initiation of malignancy that leads to uncontrolled cell death in cancer cells. Whereas, some species of ROS can influence various activities at the cellular level that include cell proliferation. This review highlights the genesis of ROS within cells by various routes and their role in cancer therapies.

scholarly journals cis-Urocanic Acid Enhances Prostaglandin E2 Release and Apoptotic Cell Death via Reactive Oxygen Species in Human Keratinocytes

2011 ◽  
Vol 131 (6) ◽  
pp. 1262-1271 ◽  
Author(s):  
Kazuyo Kaneko ◽  
Susan L. Walker ◽  
Joey Lai-Cheong ◽  
Mary S. Matsui ◽  
Mary Norval ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Prostaglandin E2 ◽  
Apoptotic Cell ◽  
Reactive Oxygen ◽  
Human Keratinocytes ◽  
Urocanic Acid ◽  
Apoptotic Cell Death ◽  
Oxygen Species

scholarly journals Green-Synthesized Silver Nanoparticles Induced Apoptotic Cell Death in MCF-7 Breast Cancer Cells by Generating Reactive Oxygen Species and Activating Caspase 3 and 9 Enzyme Activities

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ikram Ullah ◽  
Ali Talha Khalil ◽  
Muhammad Ali ◽  
Javed Iqbal ◽  
Waqar Ali ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Silver Nanoparticles ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Reactive Oxygen ◽  
Apoptotic Cell Death ◽  
Oxygen Species ◽  
Cell Viability Assay ◽  
Mcf 7

Silver nanoparticles are among the most significant diagnostic and therapeutic agents in the field of nanomedicines. In the current study, the green chemistry approach was made to optimize a cost-effective synthesis protocol for silver nanoparticles from the aqueous extract of the important anticancer plant Fagonia indica. We investigated the anticancer potential and possible involvement of AgNPs in apoptosis. The biosynthesized AgNPs are stable (zeta potential, -16.3 mV) and spherical with a crystal size range from 10 to 60 nm. The MTT cell viability assay shows concentration-dependent inhibition of the growth of Michigan Cancer Foundation-7 (MCF-7) cells (IC50, 12.35 μg/mL). In addition, the fluorescent microscopic analysis shows activation of caspases 3 and 9 by AgNPs that cause morphological changes (AO/EB assay) in the cell membrane and cause nuclear condensation (DAPI assay) that eventually lead to apoptotic cell death (Annexin V/PI assay). It was also observed that AgNPs generate reactive oxygen species (ROS) that modulate oxidative stress in MCF-7 cells. This is the first study that reports the synthesis of a silver nanoparticle mediated by Fagonia indica extract and evaluation of the cellular and molecular mechanism of apoptosis.

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