Kidney toxicity adaptive responses

Renal Issues. The parent CDs can all show a toxic effect on the kidney when given parenterally. The nephrotoxicity of a- and p-CD manifests itself as a series of alterations in the organelles of the proximal tubule cells. ° The toxicity is initially expressed as an increase in apical vacuoles, which is typical of an adaptive response tothe excretion of osmotic agents at extremely high concentrations. This effect reverses upon discontinuation of CD administration. However, there are also other cellular changes not typical of... 

Rat kidney cells adapted to growth in 5 and 10//M Pb(N03)2 become resistant to challenge with otherwise toxic Pb(II) concentrations. This resistance is associated with de novo protein synthesis. A large number of new proteins are synthesized within 6h after the cells are exposed to Pb(II) (Hitzfeld et al. 1989). The C6 rat glioma cell line also shows an adaptive response to lead (Lake et al. 1980) and a similar response has been reported for human cells (Skreb et al. 1981). We have recently identified an inducible mechanism for arsenite resistance, with cross-resistance to arsenate and antimonite, in Chinese hamster V79 cells (Wang and Rossman 1993). This inducible response is different from the heat shock response (Wang et al. 1994). The reader is referred to Chaps. 10, 14, 15, and 17 in this volume for more information on metal-induced responses. 

Our questions broadened to consider how the transport and metabolic capabilities of these aquatic species compare with those of mammalian species. One reason for asking such a question is to assess whether the presence or absence of these capabilities alters the ability of fish to survive in toxic environments. Survival mechanisms fall into two catagories - behavioral and physiologic. An example of a behavioral mechanism could be as simple as a fish avoiding that area of a stream which contains toxic quantitites of phenol. When external perturbations caused by pollutants are small, homeostatic mechanisms such as those of the liver and kidney, allow fish to adapt to the body of water in which they exist. The problem then is related to defining the limits to which homeostatic phenomena can be stressed in aquatic species. An important reason to establish such information in fish is that bodies of water are the "ultimate sink" for a number of pollutants (12). Thus, while a behavioral response such as removing itself from a toxic environment is invariably available to a mammalian species, this type of response is impossible for a fish if a toxic xenobiotic occurs uniformly throughout an entire body of water. 

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