Copper is an essential element needed for many physiological processes. But at high concentrations copper is toxic, so homeostatic mechanisms are required to regulate internal levels of copper. Fish, unlike most other vertebrates,are exposed to copper both in the diet and the external environment, and copper can cause changes in the fish's ionoregulation, olfaction and swimming performance. Exposure to copper also induces a stress response: the release of the stress hormone cortisol, which, in turn, has indirect toxic effects. Yet recent research suggests that low levels of cortisol actually protect fish from the direct effects of copper exposure. To fully understand the toxicity of copper, it has become necessary to unravel the interactions between plasma cortisol levels and copper toxicity.
In a previous study, De Boeck and colleagues demonstrated that cortisol protects fish against copper-induced decreases in the ionoregulatory enzyme Na+/K+-ATPase. Decreased gill Na+/K+-ATPase activity is one of the major ways in which copper disrupts ionoregulation. If cortisol can protect fish against this direct effect of copper toxicity, can it also prevent the accumulation of copper in tissue? Here, the authors investigated the effect of cortisol on copper accumulation in internal organs and also on a measure of the more indirect stress response; the production of heat shock proteins, which protect the fish against cellular stress during copper exposure.
Plasma cortisol levels were first elevated in common carp by feeding them a cortisol-spiked diet. Once the carp had elevated plasma cortisol concentrations, they were exposed to waterborne copper.
The team found that feeding carp a cortisol-spiked diet had a time-dependent effect on copper accumulation. During four hours of copper exposure, fish that had been pre-treated with cortisol accumulated copper in the gills and liver at a slower rate than the fish that had simply been exposed to copper. But after 96 hours of exposure this was reversed, and the cortisol-fed fish now accumulated more copper in their gills and liver than the fish that had received a normal diet. The authors hypothesise that increased ion transport, caused by elevated cortisol concentrations, could initially protect the fish from copper by temporarily easing copper's toxic effects on ionoregulation.
However, longer cortisol exposures eliminate this protective effect, and increased circulating concentrations of cortisol also create a higher possibility for toxic effects. They found that cortisol treatment before copper exposure decreased the heat shock protein response, thus reducing protection against cellular stress during copper exposure.
De Boeck and colleagues have highlighted the interaction between circulating levels of cortisol and copper toxicity. Cortisol initially protects against, but eventually stimulates, copper accumulation. In addition to their earlier work, which demonstrates the protective effects of cortisol against ionoregulatory disturbances, they have now shown that cortisol eventually results in greater tissue copper accumulation and reduces protection against cellular stress. This study demonstrates the importance of considering the effects of the animal's physiology on metal toxicity as well as the effects of metal toxicity on physiology.