Post by beebs on Sept 24, 2012 17:28:30 GMT -5
Excerpt from a brilliant article about
oxidative stress, ROS, free radicals,
and implications of medications, its role
and gene mutation:
....../
"3. Drug-Induced Oxidative Stress as a Mechanism of ToxicityDrug-induced oxidative stress is implicated as a mechanism of toxicity in numerous tissues and organ systems, including liver, kidney, ear, and cardiovascular and nervous systems. Well-characterized drugs associated with adverse events to which oxidative stress may contribute, including examples of cancer therapies, non-steroidal anti-inflammatory drugs (NSAID), antiretroviral agents, antipsychotics, and analgesics, as illustrated in Table 1. Though by no means, a comprehensive list, the examples in Table 1 serve to illustrate the potential for mechanistically distinct therapies to cause diverse toxicities with oxidative stress as a key contributor.tab1Table 1: Examples of toxicities associated with drug-induced oxidative stress.The extent to which mechanisms of drug-induced oxidative stress have been characterized varies. Metabolism of a drug may generate a reactive intermediate that can reduce molecular oxygen directly to generate ROS, as discussed below for doxorubicin. Chlorpromazine is an interesting example as photoactivation in skin is considered likely to lead to cutaneous phototoxicity (sunburn-like reaction and hyperpigmentation), which is a well-know adverse event associated with this compound [58]. Photodechlorination converts chlorpromazine to an excited state with subsequent energy transfer to molecular oxygen and generation of both excited singlet oxygen and superoxide species. These species may then react with DNA and macromolecules as described above and trigger adaptive or toxic responses in the skin as a result. For other drugs, there is evidence of elevation in cellular ROS in response to drug exposure, and evidence implicates ROS and oxidative stress in toxicity even if the mechanisms by which ROS are generated are characterized less fully. In this section, we discuss further the evidence for involvement of oxidative stress in drug-induced toxicities, using the examples of doxorubicin, azidothymidine, and cisplatin. In Figure 3, the common mechanisms by which oxidative stress in response to treatment with these drugs can lead to tissue-specific toxicities are presented."
Read article: www.hindawi.com/journals/jt/2012/645460/