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

Abstract

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.

Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy

“…Postulated explanations are enhanced neural cell death and decreased cell division [28], due to crossing of the bloodbrain barrier by certain chemotherapeutic agents and increased levels of oxidative stress [29]. Cell death however is less likely to explain the smaller volume, since it is considered irreversible and therefore contradictive to the partial recovery of local gray matter reductions that were reported in a longitudinal study after the effects of chemotherapy.…”

Noninvasive and Quantitative Assessment of the Function of Multidrug Resistance-Associated Protein 1 in the Living Brain

“…MRP1 has an unusually broad substrate specificity and can transport not only hydrophilic compounds such as GSH conjugates but also numerous hydrophobic compounds including therapeutic drugs (Loscher and Potschka, 2005b). Additionally, it has been reported that a chemotherapeutic agent affects MRP1 expression in the mice brain (Joshi et al, 2005). Therefore, the in vivo quantitative assessment of brain MRP1 function is useful for examining the alteration of MRP1 related to brain diseases and for directly evaluating the effect on MRP1 caused by drugs including modulators used to improve brain drug delivery.…”

Toxicity assessment of contaminated soils from a mining area in Northeast Italy by using lipid peroxidation assay

“…Moreover, heavy metals induce oxidative stress by generation of hydrogen peroxide, superoxide radical, hydroxyl radical and singlet oxygen, collectively termed reactive oxygen species (ROS) (Verma and Dubey, 2003). Many organic molecules are exposed to severe damage by free radicals after high accumulation of heavy metals in plants (Alfonso and Puppo, 2009;Joshi et al, 2005). Formation of ROS in cells is associated with the development of many pathological states (e. g. reduced root elongation, seed germination, signaling imbalance) (Bini et al, 2008;Wahsha and Al-Jassabi, 2009).…”