Mechanism of action of dioxin-type chemicals, pesticides, and other xenobiotics affecting nutritional indexes.
The most consistent toxic effects of dioxin-type chemicals are hyperlipidemia, body weight loss (particularly body fat loss), anorexia, changes in carbohydrate metabolism, and lipid peroxidation. The biochemical systems particularly affected are lipoprotein lipases, low-density-lipoprotein receptors, glucose transporter proteins (GLUTs), vitamin C uptake, and insulin secretion. Some of these biochemical changes occur at very low doses, and some effects can last for long time periods. To provide a mechanistic explanation for such actions of dioxins, available experimental evidence has been reviewed. The most recent discovery indicates that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) directly acts with isolated cytosolic aryl-hydrocarbon (Ah) receptor under cell-free conditions even without the presence of the nucleus and is capable of activating key protein kinases that are involved in the growth factor signal-transduction pathway. The resulting activation of primary-response transcription factors in the nucleus appears to play a key role in coordinating vital cell program shifts, including lipid metabolism.
Matsumura
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Department of Environmental Toxicology, University of California, Davis 95616.
D000818:Animals; D004147:Dioxins / Q000009:adverse effects*; D005506:Food Contamination; D006801:Humans; D009752:Nutritional Status / Q000187:drug effects*; D010575:Pesticides / Q000009:adverse effects*; D015262:Xenobiotics / Q000009:adverse effects*
D004147:Dioxins; D010575:Pesticides; D015262:Xenobiotics