Unifying mechanism for metals in toxicity, carcinogenicity and therapeutic action: integrated approach involving electron transfer, oxidative stress, antioxidants, cell signaling and receptors.
This comprehensive review of biometals involves the unifying theme of electron transfer, reactive oxygen species, and oxidative stress (OS) applied to toxicity, carcinogenicity, and therapeutic action. The beneficial effect of antioxidants supports the participation of OS. The metals involved are mainly in the heavier category. An important aspect is the favorable reduction potential exhibited by the bioactive materials that permits redox cycling in vivo with the generation of oxy radicals. The basic mechanistic theme is applicable to other electron transfer (ET) functionalities. Appreciable evidence indicates the participation of cell signaling in various ways. Also, a simplifying framework is provided based on radical species and electrochemistry (ET and molecular electrostatic potential). This review also discusses receptor participation with focus on binding to proteins. Resultant physiological effects are summarized. The overview provides an integrated approach to metal bioactivation.
Department of Chemistry, San Diego State University, San Diego, California 92182-1030, USA. pkovacic@sundown.sdsu.edu
Peter
P
Kovacic
Ratnasamy
R
Somanathan
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004579:Electron Transport; D006801:Humans; D008670:Metals / Q000009:adverse effects*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction
D000975:Antioxidants; D008670:Metals; D011956:Receptors, Cell Surface