Drug-Induced Oxidative Stress and Toxicity

Table 1

Examples of toxicities associated with drug-induced oxidative stress.

Therapeutic class	Drug	Example toxicities	Evidence for oxidative stress
Antineoplastic (anthracycline)	Doxorubicin	Cardiac toxicity	Reduction of doxorubicin to free radical increases ROS in cardiomyocytes. Lipid peroxidation, mitochondrial dysfunction, apoptosis	[111, 112]
Antiretroviral	AZT	Skeletal myopathy, cardiac toxicity	Increased ROS and NOS (peroxide and peroxynitrate). Overexpression of superoxidase dismutase/catalase protects against toxicity, apoptosis	[86, 113]
Anti-inflammatory	Diclofenac	Nephrotoxicity, hepatotoxicity	Oxidative stress generated by a cation radical or redox cycling of intermediates derived from hydroxylation. Multifactorial perturbations in mitochondrial dysfunction	[114, 115]
Analgesia	Paracetamol	Hepatotoxicity	Formation of reactive metabolite, depletion of glutathione, activation of proapoptotic proteins. Mitochondrial dysfunction, inflammation	[116]
Antineoplastic (platinum)	Cisplatin	Nephrotoxicity, ototoxicity	Increases in superoxide anion, hydrogen peroxide, and hydroxyl radical. Depletion of antioxidants GSH-peroxidase and GSH-reductase. Mitochondrial dysfunction, apoptosis	[93, 97, 99, 117]
Antipsychotic	Chlorpromazine	Dermal toxicity (due to phototoxicity)	Generation of singlet oxygen and superoxide in response to UVA/B irradiation	[102]