TY - JOUR
T1 - Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin
T2 - Insight into chemobrain
AU - Joshi, Guraraj
AU - Sultana, Rukhsana
AU - Tangpong, Jitbanjong
AU - Cole, Marsha Paulette
AU - St. Clair, Daret K.
AU - Vore, Mary
AU - Estus, Steven
AU - Butterfield, D. Allan
N1 - Funding Information:
This work was supported in parts by grants from NIH to DAB [AG-10836; AG-05119], and DSC [AG-05119; CA-80152; CA-94853].
PY - 2005/11
Y1 - 2005/11
N2 - 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 peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated 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. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.
AB - 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 peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated 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. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.
KW - Adriamycin
KW - Cancer chemotherapeutics
KW - Chemobrain
KW - Multidrug resistance-associated protein 1
KW - Oxidative stress
KW - Somnolence
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U2 - 10.1080/10715760500143478
DO - 10.1080/10715760500143478
M3 - Article
C2 - 16298740
AN - SCOPUS:27744462197
SN - 1071-5762
VL - 39
SP - 1147
EP - 1154
JO - Free Radical Research
JF - Free Radical Research
IS - 11
ER -
