Collateral Damage in Cancer Chemotherapy: Oxidative Stress in Nontargeted Tissues

Abstract

Injury to nontargeted tissues in chemotherapy often complicates cancer treatment by limiting therapeutic dosages of anticancer drugs and by impairing the quality of life of patients during and after treatment. Oxidative stress, directly or indirectly caused by chemotherapeutics as exemplified by doxorubicin, is one of the underlying mechanisms of the toxicity of anticancer drugs in noncancerous tissues, including the heart and brain. A comprehensive understanding of the mechanisms of oxidative injury to normal tissue will be essential for the improvement of strategies to prevent or attenuate the toxicity of chemotherapeutic agents without compromising their chemotherapeutic value.

Doxorubicin increases the susceptibility of brain mitochondria to Ca2+-induced permeability transition and oxidative damage

“…Free radical-mediated oxidative stress has been proposed as a potential mechanism underlying DOX toxicity in the brain [4]. In accordance, we observed that DOX treatment increases TBARS levels (Fig.…”

“…However, much less is known about the effects of DOX treatment in the brain. Although previous studies indicate that cancer patients under DOX therapy present signs of cognitive decline [4], the mechanisms underlying these cognitive alterations remain unknown.…”

“…Several studies in breast cancer survivors and other patients undergoing DOX-based chemotherapy have reported persistent changes in cognitive functions, including memory loss and difficulty in the performance of daily life tasks [4]. Despite the well-known side effects of DOX treatment in the heart, little is known about its effects in the brain.…”

“…The mechanisms underlying these events seem to be linked to an increased production of reactive oxygen species (ROS) and oxidative damage [3]. Oxidative stress results from an imbalance between the generation of ROS and reactive nitrogen species and their removal by the cellular antioxidant system [4] and has been implicated in many neurodegenerative disorders [5,6].…”

“…The mechanisms underlying these events seem to be linked to an increased production of reactive oxygen species (ROS) and oxidative damage [3]. Oxidative stress results from an imbalance between the generation of ROS and reactive nitrogen species and their removal by the cellular antioxidant system [4] and has been implicated in many neurodegenerative disorders [5,6].Several studies in breast cancer survivors and other patients undergoing DOX-based chemotherapy have reported persistent changes in cognitive functions, including memory loss and difficulty in the performance of daily life tasks [4]. Despite the well-known side effects of DOX treatment in the heart, little is known about its effects in the brain.…”