Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: Insight into chemobrain

  title={Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: Insight into chemobrain},
  author={Gururaj Joshi and Rukhsana Sultana and Jitbanjong Tangpong and Marsha P Cole and Daret K. St. Clair and Mary Vore and Steven Estus and David Allan Butterfield},
  journal={Free Radical Research},
  pages={1147 - 1154}
Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers. ADR is a quinone-containing anthracycline chemotherapeutic and is known to produce reactive oxygen species (ROS) in heart. Application of this drug can have serious side effects in various tissues, including brain, apart from the known cardiotoxic side effects, which limit the successful use of this drug in treatment of cancer. Neurons treated with ADR demonstrate significant protein oxidation and lipid… 

The effect of the nitroxide pirolin on oxidative stress induced by doxorubicin and taxanes in the rat brain.

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.

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

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.

Protection of multiple antioxidants Chinese herbal medicine on the oxidative stress induced by adriamycin chemotherapy

It is demonstrated that adriamycin chemotherapy could cause oxidative stress to the whole body, on which multiple antioxidants based on the theory of ‘multiple antioxidant chain’ had effective protection.

Role of inflammatory, oxidative, and ER stress signaling in the neuroprotective effect of atorvastatin against doxorubicin-induced cognitive impairment in rats.

Atorvastatin (ATV) exhibited neuroprotective properties against DOX-induced cognitive impairment which could possibly be attributed to their anti-inflammatory, antioxidant, and anti-apoptotic effects in the brain.

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”)

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.

Adriamycin-induced, TNF-α-mediated central nervous system toxicity




Nitric oxide and oxidative stress in brain and heart of normal rats treated with doxorubicin: Role of aminoguanidine

AG treatment failed to prevent the excessive release of cardiac enzymes; however, it alleviated the adverse effects of DOX in heart and brain, and it is recommended that, maintenance of the endogenous antioxidant, GSH, and regulation of calcium homeostasis must be considered, rather than NO formation, to guard against DOX‐induced toxicity.

Adriamycin induces protein oxidation in erythrocyte membranes.

Results are consistent with the notion that oxidative modification of membrane proteins may contribute to the development of the acute adriamycin-mediated toxicity.

Protective Effect of the Xanthate, D609, on Alzheimer's Amyloid β-peptide (1–42)-induced Oxidative Stress in Primary Neuronal Cells

The results suggest that D609 exerts protective effects against Aβ(1–42) toxicity by modulating oxidative stress, and may be of importance for the treatment of AD and other oxidative stress-related diseases.

Oxidatively Modified GST and MRP1 in Alzheimer’s Disease Brain: Implications for Accumulation of Reactive Lipid Peroxidation Products

The data suggest that 4-hydroxy-2-trans-nonenal may be an important mediator of oxidative stress-induced impairment of this detoxifying system and may thereby play a role in promoting neuronal cell death in AD.

Cytoprotective agents for anthracyclines.

  • R. Dorr
  • Biology, Chemistry
    Seminars in oncology
  • 1996
In tumor-bearing mice, amifostine reduces the lethality of high doses of doxorubicin without affecting antitumor activity, and in vitro studies in neonatal rat heart cells have shown direct evidence of anthracycline cardioprotection for both am ifostine and WR-1065.

A Role for 4‐Hydroxynonenal, an Aldehydic Product of Lipid Peroxidation, in Disruption of Ion Homeostasis and Neuronal Death Induced by Amyloid β‐Peptide

The data suggest that HNE mediates Aβ‐induced oxidative damage to neuronal membrane proteins, which, in turn, leads to disruption of ion homeostasis and cell degeneration.

Peroxynitrite‐Induced Alterations in Synaptosomal Membrane Proteins

Investigation of damage to brain neocortical synaptosomal membrane proteins and the oxidation‐sensitive enzyme glutamine synthetase caused by exposure to ONOO shows that ONOO‐ can oxidatively modify both membranous and cytosolic proteins, affecting both their physical and chemical nature.

Cell-permeable superoxide dismutase and glutathione peroxidase mimetics afford superior protection against doxorubicin-induced cardiotoxicity: the role of reactive oxygen and nitrogen intermediates.

It is suggested that the SOD mimetic MnTBAP prevents DOX-induced damage to cardiomyocytes and that the GPx mimetic ebselen synergistically enhanced the cardioprotection afforded by Mn TBAP.

Doxorubicin-induced Apoptosis in Endothelial Cells and Cardiomyocytes Is Ameliorated by Nitrone Spin Traps and Ebselen

It is concluded that nitrone spin traps and ebselen inhibit the DOX-induced apoptotic signaling mechanism and that this antiapoptotic mechanism may be linked in part to the inhibition in formation or scavenging of hydrogen peroxide.