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Mechanism of action of dioxin-type chemicals, pesticides, and other xenobiotics affecting nutritional indexes Matsumura FAm J Clin Nutr 1995[Mar]; 61 (3 Suppl): 695S-701SThe 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.|Animals[MESH]|Dioxins/*adverse effects[MESH]|Food Contamination[MESH]|Humans[MESH]|Nutritional Status/*drug effects[MESH]|Pesticides/*adverse effects[MESH]|Xenobiotics/*adverse effects[MESH] |
