Lipid peroxidation and pharmaceutical drugs

There exists a multitude of pharmaceutical drugs which effects include the formation of oxidants and, therefore increased lipid peroxidation or which at least deteriorate the redox balance within cells, tissues or organs. In many of those cases, the generated oxidants are an important part of the drug efficiency. Well known examples of those drugs and xenobiotics are anticancerogenic drugs (chemotherapeutics), antihelminthics, dermatics, tuberculostatics and various antibiotics. In anticholinergics and spasmolytics an increased generation of oxidants and lipid peroxides seems to be rather a side effect than a specific pharmacological effect. That seems true also for all xenobiotics stimulating the catecholamine formation. The increased free radical generation and lipid peroxidation by chemotherapeutic drugs and cytostatics, by many antibiotics, tuberculostatics, and dermatics contributes to therapy of different types of cancer, microbially induced infectious diseases – by bacteria, viruses, or fungi – autoaggression, or psoriasis. Doxorubicin/daunorubicin is an example for anthracyclin-antibiotics used in the therapy of malignant tumors such as breast and lung tumors, gynecological sarcomas, lymphomas, and hepatocellular carcinoma (HCC). Within its fine mechanisms of this substance one finds intercalant transcription inhibiting effectivity, inhibition of topoisomerase II activity, and promoting an overwhelming formation of oxidants and lipid peroxidation products. Last mechanism leads also to strong side effects of doxorubicin such as depression of the bone marrow and cardiotoxicity. In contrast other pharmaceutical drugs reduce the concentration of oxidants or even directly deliver antioxidants, such as antiallergics, nootropics (antidementives), geriatrics, antiphlogistics, prostaglandins and prostacyclins such as iloprost, drugs influencing gout or hyperuricemia such as inhibitors of purine degradation, roborantia and vitamine preparatives, also anticoagulative acting drugs, and hypnotics. The use of GSH can be useful, since the dysfunction of the GSH redox system appears to cause a variety of diseases including neurodegenerative disorders. However, the effectiveness of GSH as therapeutic agent is limited because of its low bioavailability. Another aspect of the formation of oxidants and increased lipid peroxidation during and after application of pharmaceutical drugs is the detoxification of drugs preferably by the liver. The metabolic reactions involved in the detoxification of drugs and further xenobiotics present one of the main sources for the generation of oxidants in humans and animals treated with pharmaceutical drugs. The cytochrome P450 systems plays an important role within total oxygen radical and oxidant generation in human body.