The results of studies of anabolic action of 20- hydroxyecdysone in experiments on laboratory animals and the possible explanation (existing in the modern scientific literature) of the mechanism of this phenomenon are discussed. The features of adaptogenic effect of phytoecdysteroids, polyhydroxylated sterols, which are analogs of hormones of molting and metamorphosis of arthropodas, and are structurally similar to glucocorticoids on the example of the most widely studied phytoecdysteroid- 20- hydroxyecdysone-are described. The hypothetical mechanism of action: adaptogens are prostressors, reducing excessive increase of stress mediators in the following stress exposure. Its administration can help to achieve non-specific state of high resistance. In the review the presentation about plant adaptogens-biologically active compounds is given. The application of the in vitro/in vivo approach used in this study is discussed in relation to modeling of nonadditive interactions The result of such interactions can be toxicity due to inappropriate or exaggerated hormonal signaling. Taken together, these results demonstrate that xenobiotics, such as tributyltin, can interact with RXR to influence gene expression regulated by the heterodimeric partner to RXR. Continuous, prolonged exposure of maternal daphnids to concentrations of tributyltin resulted in mortality concurrent with molting. Further, exposure of daphnids to tributyltin enhanced the inductive effects of 20- hydroxyecdysone on expression of the 20- hydroxyecdysone-inducible gene HR3. Tributyltin exaggerated this effect of exogenous 20- hydroxyecdysone. Exposure of daphnids to elevated concentrations of 20- hydroxyecdysone caused premature and incomplete ecdysis resulting in death. Electrophoretic mobility shift assays revealed that tributyltin did not enhance the activity of 20- hydroxyecdysone by increasing binding of the receptor complex to a DR-4 DNA-binding site. However, tributyltin, in combination with the daphnid EcR ligand 20- hydroxyecdysone, caused concentration-dependent, synergistic activation of the RXR:EcR reporter. Using reporter gene assays, we demonstrated that RXR, alone, is activated by a variety of ligands including tributyltin, whereas RXR:EcR heterodimers were not activated by tributyltin. We hypothesized that tributyltin would elicit toxicity in daphnids (Daphnia magna) by exaggerating physiological responses to 20- hydroxyecdysone signaling via synergistic activation of the retinoid X receptor (RXR):ecdysteroid receptor (EcR) complex. The development of effective means of predicting the toxicity of chemical mixtures requires an understanding of how chemicals interact to produce nonadditive outcomes (e.g., synergy). One of the great challenges facing modern toxicology is in predicting the hazard associated with chemical mixtures. Wang, Ying H Kwon, Gwijun Li, Hong Leblanc, Gerald A Tributyltin synergizes with 20- hydroxyecdysone to produce endocrine toxicity.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |