Page 430 - The Toxicology of Fishes

410 The Toxicology of Fishes

+
activity (Li et al., 1996), the opposite effect was expected, as reduction of Na efflux points to increased
+
+
tubular reabsorption of Na , for which Na /K -ATPase is a driving force. This phenomenon was explained
+
+
as a physiological response of the kidneys to compensate the impairment of branchial Na uptake (Grosell
et al., 1998). This indicates that the renal Na-/K -ATPase activity provides better protection against
+
copper than the branchial activity, and this is in agreement with the low renal accumulation and excretion
rates for copper. Few studies are available on the physiological aspects of renal hydromineral function
such as urine flow and renal ion excretion rates. Collection of such data requires cannulation techniques
that are complicated and, because they are extremely stressful to the fish, often lead to results that are
biased by the experimental procedures; thus, a proper evaluation of the effects of toxic chemicals on the
kidneys is even more complicated than on gills and intestine.

Toxic Agents and Endocrine Control of Osmoregulation

Good evidence from fishes suggests that toxic agents can affect neuroendocrine cells and in this way
interfere with neuroendocrine control processes, including osmoregulation (Hontela et al., 1993). The
cell types that have received most attention in this respect are the prolactin cells and adrenocorticotropic
hormone (ACTH) cells in the pituitary gland and the interrenal cells producing cortisol. Prolactin is an
important hormone for the control of permeability to water and ions in the gills, intestine, and renal
tubules. Activation of prolactin cells has been frequently observed in fish exposed to toxic agents and
has been generally interpreted as a compensatory response to the disturbance in the permeability
characteristics of these epithelia by toxicants (see review by Wendelaar Bonga and Pang, 1989). ACTH
is an important secretagog of cortisol (Balm and Pottinger, 1999). The latter hormone is not only one
+
+
of the primary stress hormones in fish (see under Gills) but also an important stimulator of Na /K -
ATPase activity in gills, intestine, and kidneys. The multiple functions of this hormone clearly demon-
strate the intimate relationship between the stress response and osmoregulation in fish. These functions
of cortisol explain the stimulation of cortisol release that has been frequently reported for fish exposed
to toxic agents (see reviews by Hontela, 1997; Wendelaar Bonga, 1997).
Norris et al. (1997) reported that the hypothalamo–pituitary–interrenal (HPI) axis of feral brown trout
is activated in fish from sites contaminated with cadmium and zinc. They reported a higher number of
immunoreactive neurons in the hypothalamus than in fish from control sites and further observed
hypertrophy and hyperplasia in the interrenal cells of the fish from contaminated water; however, the
relationship between some toxic agents and cortisol secretion may be more complicated and includes
interference with the secretion of cortisol and ACTH. The interrenal tissue of yellow perch from a site
contaminated by a mixture of heavy metals and organic contaminants secreted significantly less cortisol
in response to a standardized pulse of ACTH than the interrenal tissue of fish from an unpolluted reference
site (Brodeur et al., 1998).
Field studies on the effects of a mixture of contaminants (including heavy metals and PCBs) showed
endocrine dysfunction in fish from natural water contaminated with a mixture of pollutants when
compared with fish from an unpolluted reference site (Hontela et al., 1992, 1995). Feeding low levels
of PCB 169 to rainbow trout stimulated and higher levels impaired the production of cortisol, cortisone,
and other metabolites by interrenal cells as determined in vitro (Freeman et al., 1984). Short-term
exposure (5 days) of Mozambique tilapia to PCB 126 did not influence branchial, renal, or intestinal
+
+
Na /K -ATPase activity, nor did it evoke a stress response, as was concluded from the absence of a rise
in plasma cortisol or glucose levels; however, when the fish were exposed to acute sampling stress,
plasma cortisol levels were lower in PCB-fed fish than in controls (Figure 8.5). The interrenal cells of
PCB fed fish proved to be less responsive to ACTH or cAMP stimulation in vitro, indicating direct
toxic effects on the interrenal cells, rather than secondary effects via disturbance of hydromineral
imbalance or stimulation of mixed-function oxygenase systems involved in steroid catabolism. (Quabius
et al., 1997). Vijayan et al. (1997) observed an impaired ability to elicit a cortisol response in stressed
trout exposed to PCB 77 and suggested that this might be caused by the enhanced hepatic cortisol
clearance in these fish. Given the importance of cortisol for osmoregulation in fish, any interference
with the secretion of cortisol and its secretagogs such as ACTH may be expected to have an effect on