Dermal toxicity and environmental contamination: electron transfer, reactive oxygen species, oxidative stress, cell signaling, and protection by antioxidants.
Large numbers of chemicals are known to produce diverse types of skin injury, and these substances fit into a wide variety of both organic and inorganic chemical classes. Skin contact with toxins is difficult to avoid, because they are widely distributed, e.g., in industrial substances, agricultural chemicals, household products, and plants. Although various hypotheses have been advanced, there is no universal agreement as to how dermal toxins act to produce their effects. In this review, we provide evidence and numerous literature citations to support the view that oxidative stress (OS) and electron transfer (ET) comprise a portion of a key mechanism, and perhaps unifying theme that underlie the action of dermatotoxins. We apply the concept that ET and OS are key elements in the induction of dermatotoxic effects to all of the main classes of toxins, and to other toxins, as well. We believe it is not coincidental that the vast majority of dermatotoxic substances incorporate recurrent ET chemical functionalities (i.e., quinone, metal complexes, ArNO2, or conjugated iminium), either per se or as metabolites; such entities potentially give rise to reactive oxygen species (ROS) by redox cycling. However, in some categories, wherein agents cause dermal damage, e.g., peroxides and radiation, it appears that ROS are generated by non-ET routes. As expected, if ET and oxidative process do constitute the mechanistic framework by which most dermal toxins act, then antioxidants (AOs), if present, should prevent or mitigate effects. This is exactly what has been discovered to occur. Because ET and OS either cause or contribute to dermal toxicity, and AOs may offer protection therefrom, policy makers and researchers may be better positioned to prevent human dermatotoxicity.
Kovacic
Peter
P
Department of Chemistry, San Diego State University, San Diego, CA 92182-1030, USA. pkovacic@sundown.sdsu.edu
Somanathan
Ratnasamy
R
D000818:Animals; D003875:Drug Eruptions / Q000378:metabolism*; D004579:Electron Transport; D004785:Environmental Pollutants / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D004785:Environmental Pollutants; D017382:Reactive Oxygen Species