Nephrotoxins: Widespread role of oxidative stress and electron transfer

Kidney toxicity comprises an important type of hospital admission with associated high costs. Large numbers of chemicals are involved comprising a wide log variety of classes, both organic and inorganic. These include therapeutic drugs, radiocontrast agents, carcinogens, metals, abused drugs, and industrial chemicals. This review provides extensive evidence for participation of oxidative stress (OS) and electron transfer (ET) as a unifying framework. Application is made to all the main classes of nephrotoxins, in addition to many miscellaneous types. We believe it is not coincidental that the vast majority of these substances incorporate ET functionalities (quinone, metal complex, ArNO2, or conjugated iminium) either per se or in metabolites, potentially giving rise to reactive oxygen species (ROS) by redox cycling. Some categories, e.g., radiation, radiocontrast agents, and peroxides, appear to generate OS by non-ET routes, For completeness, other theories are also addressed; a multifaceted approach appears the most logical. The ET-OS viewpoint should increase understanding and contribute to prevention, e.g., use of antioxidants.