Adverse drug reactions and reactive oxygen species.

Adverse drug reactions represent a major source of morbidity in hospitalized- and outpatients. Adverse drug reactions may affect the function of any organ or system. Due to their clinical nonspecificity adverse drug reactions are often difficult to be recognized. The clinical manifestation, the type and severity of adverse drug reactions vary a great deal depending on patient- and drug-related factors. In recent years growing evidence has emerged implicating involvement of free radicals and reactive oxygen species in chronic degenerative diseases and in acute conditions, such as stroke and infection. The review focuses on the role of reactive oxygen species in the pathogenesis of drug-induced disease with special reference to hepatotoxicity, nephrotoxicity and allergic disease. The participation of reactive oxygen species in the development of adverse drug reactions induced by special drug classes (non-steroidal anti-inflammatory drugs, anti-infective agents, cytostatics) is described. Results from studies on animals and humans reveal the putative implication of oxidative stress in drug-induced disease states.

Two spin labeled triazenes: relationship between biochemical and biological activities.

Biochemical and biological activities of two recently synthesized spin labeled triazenes, containing the nitroxyl free radical moiety at different places of the triazene structure have been studied and compared with those of the antitumor drug Dacarbazine (DTIC). Tissue distribution of the triazenes was investigated in vitro in organ homogenates, tumor (B16 melanoma) and blood of C57BL mice using the electron paramagnetic resonance (EPR) method. The spin labeled triazenes were mainly localized in the tumor and in the brain. Normal leucocites, YAC-1 mNK target Moloney lymphoma cells and B16 melanoma cells were treated with spin labeled triazenes in vitro and the effects on cell viability were compared. Spin labeled 3,3-dimethyl triazene with nitroxyl radical as a substituent in the benzen ring was more cytotoxic to B16 melanoma cells than to YAC-1 Moloney lymphoma cells and normal leucocites in comparison to the spin labeled monomethyl triazene. The spin labeled derivatives were assessed with low toxicity for BDF1 mice hybrids in vivo. These results could be interpreted in terms of a possible correlation between tissue distribution and the selective antimelanoma activity of the spin labeled triazenes.