Oxidative stress occurs when there is a disturbance in the balance between the production of reactive oxygen species (ROS) and the cell's antioxidant defenses. Exposure to drugs can induce the formation of excess ROS or lower the antioxidant defense systems of the cell. Direct drug metabolism may cause the formation of ROS or other radical species through the oxidative or reductive metabolism of the drug. Other mechanisms can disrupt essential detoxification enzymes, such as superoxide dismutase and glutathione peroxidase in mitochondria, which become overtaxed in stressing conditions. Excessive oxidant species can cause oxidative damage to mitochondrial DNA and proteins, and membrane lipids, which alter cell structure and function. Oxidative damage also aggravates mitochondrial dysfunction and creates more ROS production leading to aberrant cell bioenergetics and cell death.

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