The triangle of death of neurons: Oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment ("chemobrain") involving TNF-α.

@article{Ren2019TheTO,
  title={The triangle of death of neurons: Oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment ("chemobrain") involving TNF-$\alpha$.},
  author={Xiaojia Ren and Jeriel T. R. Keeney and Sumitra Miriyala and Teresa J. Noel and David K. Powell and Luksana Chaiswing and Subbarao Bondada and Daret K. St. Clair and David Allan Butterfield},
  journal={Free radical biology \& medicine},
  year={2019},
  volume={134},
  pages={
          1-8
        }
}
View on PubMed
europepmc.org
32 Citations
Background Citations
5

Figures from this paper

32 Citations

Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment ("chemobrain"), a condition that significantly impairs the quality of life of many cancer survivors.
Elevated Oxidative Stress and DNA Damage in Cortical Neurons of Chemotherapy Patients.
TLDR
The study highlights the potential relevance of oxidative stress and DNA damage in the pathophysiology of CRCI and the neurotoxicity of chemotherapy as well as identifying pathways relevant to CRCI in humans.
Oxidative Stress and Cognitive Alterations Induced by Cancer Chemotherapy Drugs: A Scoping Review
TLDR
Administration of compounds with strong antioxidant effects such as N-acetylcysteine, gamma-glutamyl cysteine ethyl ester, polydatin, caffeic acid phenethyl ester and 2-mercaptoethane sulfonate sodium (MESNA) counteract both oxidative stress and cognitive alterations induced by chemotherapeutic drugs.
Dietary agents in mitigating chemotherapy-related cognitive impairment (chemobrain or chemofog): first review addressing the benefits, gaps, challenges and ways forward.
TLDR
This review focuses on the published effects of astaxanthin, omega-3 fatty acids, ginsenoside, cotinine, resveratrol, polydatin, catechin, rutin, naringin, curcumin, dehydrozingerone, berberine, C-phycocyanin, the higher fungi and polyherbal formulation Mulmina™ in mitigating cognitive impairments in preclinical models of study.
Doxorubicin-Induced Cognitive Impairment: The Mechanistic Insights
TLDR
Doxorubicin (DOX), a commonly used drug in adjuvant chemotherapy for patients with breast cancer, has been reported to induce chemo-brain through a variety of mechanisms including DNA damage, oxidative stress, inflammation, dysregulation of apoptosis and autophagy, changes in neurotransmitter levels, mitochondrial dysfunction, glial cell interactions, neurogenesis inhibition, and epigenetic factors.
Chemobrain: mitoxantrone-induced oxidative stress, apoptotic and autophagic neuronal death in adult CD-1 mice.
TLDR
In the whole brain, MTX-induced redox imbalance shown as increased endothelial nitric oxide synthase and reduced manganese superoxide dismutase expression, as well as a tendency to a decrease in glutathione levels, caused damage in the brain of adult CD-1 mice in a clinically relevant cumulative dose in areas involved in memory and cognition.
Protective effects of diallyl trisulfide (DATS) against doxorubicin-induced inflammation and oxidative stress in the brain of rats.
Donepezil Protects Against Doxorubicin-Induced Chemobrain in Rats via Attenuation of Inflammation and Oxidative Stress Without Interfering With Doxorubicin Efficacy.
TLDR
It is suggested that DPZ treatment confers potential neuroprotection against Dox-induced chemobrain, and intervention with DPZ co-treatment completely restored cognitive function by attenuating these pathological conditions induced by DOX.
Four decades of chemotherapy-induced cognitive dysfunction: comprehensive review of clinical, animal and in vitro studies, and insights of key initiating events
TLDR
This work aimed to provide a comprehensive review using PubMed as a database to assess the studies published on the field and highlight the clinical manifestations of chemobrain and the putative neurotoxicity mechanisms.
Emerging mechanistic underpinnings and therapeutic targets for chemotherapy-related cognitive impairment.
TLDR
A new understanding of the mechanistic underpinnings of CRCI has elucidated potential therapeutic interventions, including colony-stimulating factor 1 receptor inhibition, TrkB agonism, and aerobic exercise.
...
...

References

SHOWING 1-10 OF 71 REFERENCES
Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”)
TLDR
This study is the first to demonstrate the protective effects of MESNA on Dox-related protein oxidation, cognitive decline, phosphocholine (PCho) levels, and PC-PLC activity in brain and suggests novel potential therapeutic targets and strategies to mitigate CICI.
Alterations in brain antioxidant enzymes and redox proteomic identification of oxidized brain proteins induced by the anti-cancer drug adriamycin: implications for oxidative stress-mediated chemobrain
Glutathione elevation by γ‐glutamyl cysteine ethyl ester as a potential therapeutic strategy for preventing oxidative stress in brain mediated by in vivo administration of adriamycin: Implication for chemobrain
TLDR
This study test the hypothesis that, by elevating brain levels of GSH, the brain would be protected against oxidative stress in ADR‐injected mice, and results are discussed with regard to potential pharmacological prevention of brain cognitive dysfunction in patients receiving ADR chemotherapy.
2-Mercaptoethane sulfonate prevents doxorubicin-induced plasma protein oxidation and TNF-α release: implications for the reactive oxygen species-mediated mechanisms of chemobrain.
Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: Insight into chemobrain
TLDR
A significant increase in levels of protein oxidation and lipid peroxidation and increased expression of MRP1 in brain isolated from mice, 72 h post i.p injection of ADR is demonstrated.
Dysregulation of cytokine mediated chemotherapy induced cognitive impairment
Adriamycin‐mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain
TLDR
It is demonstrated that treatment with ADR led to an increased circulating level of tumor necrosis factor‐alpha in wild‐type mice and in mice deficient in the inducible form of nitric oxide (iNOSKO), and it is suggested that NO is an important mediator, coupling the effect of ADR with cytokine production and subsequent activation of iNOS expression.
Plasma TNF-α and Soluble TNF Receptor Levels after Doxorubicin with or without Co-Administration of Mesna—A Randomized, Cross-Over Clinical Study
TLDR
The extracellular anti-oxidant mesna, when co-administered during a single cycle of doxorubicin, reduced levels of TNF-α and its receptors after that cycle of therapy, demonstrating for the first time a clinical interaction between mesna and dox orubicIn, drugs often coincidentally co- Administered in multi-agent regimens.
Doxorubicin and cyclophosphamide treatment produces anxiety-like behavior and spatial cognition impairment in rats: Possible involvement of hippocampal neurogenesis via brain-derived neurotrophic factor and cyclin D1 regulation
The effect of the nitroxide pirolin on oxidative stress induced by doxorubicin and taxanes in the rat brain.
TLDR
PL, in combination with anticancer drugs, partially protected the rat brain against the toxic effects of DOX and taxanes, highlighting its potential application in protecting the brain against DOX-, DTX- and PTX-evoked OS.
...
...