Integrated approach to the mechanisms of thyroid toxins: electron transfer, reactive oxygen species, oxidative stress, cell signaling, receptors, and antioxidants.
Although considerable numbers of reviews are available on toxicity of major body organs based on electron transfer (ET), reactive oxygen species (ROS), and oxidative stress (OS), the integrated concept has been less applied to glands. This review represents an interdisciplinary approach to thyroid toxicity, involving ET, ROS, OS, cell signaling, receptors, toxicants, and beneficial effects of antioxidants (AOs). The introductory portion includes general function of the thyroid as well as the mechanism of thyroxine synthesis entailing participation of oxidative events, including the role of iodine. Various ROS, both endogenous and exogenous, are importantly involved in the diverse toxic manifestations. Discussion is centered on hydrogen peroxide and lipid peroxides. There is also treatment of receptor-ligand activity. Cell signaling participates in the various biochemical events taking place in the thyroid, both beneficial and adverse. In addition, the mechanism of cell signaling is discussed based on radicals, ET, relays, conduits, and electrochemistry. In addition to endogenous toxins, various exogenous ones are addressed, falling in diverse classes. Data indicate involvement of ET-ROS-OS in the toxic manifestations. Large numbers of reports reveal the beneficial effects of AOs in countering the toxicity, which is in accord with the mechanistic framework.
Department of Chemistry, San Diego State University, San Diego, California, USA. pkovacic@sundown.sdsu.edu
Peter
P
Kovacic
Corey
C
Edwards
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D004147:Dioxins / Q000494:pharmacology; D004563:Electrochemistry / Q000379:methods; D004583:Electrons; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007455:Iodine / Q000737:chemistry; D008024:Ligands; D008054:Lipid Peroxides / Q000737:chemistry; D008954:Models, Biological; D018384:Oxidative Stress; D019800:Phenol / Q000737:chemistry; D017382:Reactive Oxygen Species; D012276:Ricin / Q000737:chemistry; D015398:Signal Transduction; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism*
D000975:Antioxidants; D004147:Dioxins; D008024:Ligands; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D019800:Phenol; D012276:Ricin; D007455:Iodine; D006861:Hydrogen Peroxide