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.Figure 2.9 Simplified mechanism of Cd-MT renaltoxicity.Cd-MT is filtered by theglomerulus and is then transported into therenal cell via endocytosis.Free Cd2+ isreleased during lysosomal degradation,and stimulates the synthesis of MT withinthe tubule cell.As intracellular Cdconcentrations increase, the capacity forMT production is overwhelmed, andbinding to non-MT proteins can occur.Modified from Goldstein and Schnelmann(1996). Target organ toxicity in the kidney 145In both terrestrial and aquatic species, cadmium is inhibitory (in vitro and in vivo) tonumerous enzymes, including acetylcholinesterase (AChE), acid phosphatase, alkalinephosphatase, Na+, K+-ATPase, and lactate dehydrogenase.In some instances of in vivoexposure, however, increases in the activity of select kidney enzymes have beendescribed.An example is the case of the rosy barb (Barbus conchius), which showssignificant Cd-related inhibition (in vitro and in vivo) of acid phosphatase and glutamicpyruvic transaminase in kidney homogenates, whereas kidney alkaline phosphataseactivity is increased by more than 100 percent (Gill et al., 1991a).The enzymaticinhibitory activity of Cd is probably due in most cases to either binding of Cd to theenzyme or displacement of a cofactor, but species and tissue differences exist for theinhibitory mechanism of some enzymes (e.g.Na+,K+-ATPase) (Kinne-Saffran et al.,1993).Cadmium also affects kidney-related steroidogenesis in some piscine species byaltering cortisol production, a function of the inter-renal tissue.The inter-renal cells ofrainbow trout particularly seem to respond sensitively to Cd exposure, with cortisol levelsincreasing rapidly and remaining elevated during exposure to sublethal concentrations(Hontella et al., 1996).Whether Cd directly mediates this effect or whether it is anindirect effect of osmoionic disruption is unclear.However, it is possible that Cd-inducedincreases in cortisol are actually a result of calcium (Ca2+) channel blockade at the gill,leading to hypocalcemia and stimulation of inter-renal cells.Another proposedmechanism is that impaired glucose metabolism, related to renal toxicity, may altercortisol production.This idea is supported by findings of decreased kidney glycogen afterCd and Hg exposure (Srivastava, 1982).The long-term consequences of altered cortisolregulation may include effects on other hormonal systems and decreased responsivenessto stress.Chronic exposure to environmentally relevant concentrations of CdCl2 often lead toextensive renal pathologies in fish.Common carp (Cyprinus carpio) display progressivetubular necrosis at exposures of 58 g L-1 CdCl2 for several weeks (Singhal and Jain,1997).These necrotic changes (nuclear pyknosis, karyohexis, and karyolysis) are alsoassociated with glomerular alterations, loss of brush border in PI and PII segments, andincreases in intertubular space.Similar tubular necrosis and glomerular collapse havebeen documented in Puntius conchonius after sublethal exposures (Gill et al., 1989).However, a study in which stickleback (Gasterosteus aculeatus) were exposed to Cd2+concentrations as high as 6 mg L-1 described only moderate changes in tubular cells,consisting primarily of vacuolization and granulation (Oronsaye, 1989).The variability inresponse between these species is unclear, but may be related to differences in MTinduction, drinking rates, or renal transport processes.MERCURYMercury (Hg) exists naturally in high concentrations in some waterways, but its toxicityand bioaccumulative nature raise concerns for the safety of exposed organisms.In 1997,1782 mercury advisories existed for waterways in the USA (USEPA, 1998).Theseadvisories are established to warn the public of potential fish consumption hazards basedon fish muscle residue analysis.Although the primary regulatory agenda for Hg in theUSA has been driven by human heath concerns, bioconcentration and biomagnification Target organ toxicity in marine and freshwater teleosts 146of Hg by teleosts pose legitimate threats to the health of aquatic systems receiving inputsof Hg.Mercury may exist in its elemental state (Hg°2), as inorganic salts (HgCl2), and inorganic (primarily methylated) forms.The inorganic salt is primarily implicated inmammalian nephrotoxic effects, although nephrotoxicity has been noted in fish exposedto organomercurials (Gill et al.,1988).In aquatic systems, only 5 20 percent of the totalmercury exists as methylmercury (MeHg).Yet, bioaccumulation of Hg in fish occursalmost completely (> 95 percent) through the methylated forms (MeHg), with extensiveMeHg deposition in the kidneys (Watras and Huckabee, 1994).In vitro experiments with flounder (Pseudoplectonectes americanus) tubules haveshown a concentration-dependent increase in cellular injury with short-term exposure toHgCl2, MeHgCl, and parachloromercuribenzenesulfonate (PCMBS) (Trump and Jones,1975).Of these compounds, MeHg causes the most rapid histologic progression of tubulecell injury.However, the inorganic form is responsible for the most substantial decreasein chlorophenol red uptake, a measure of active transport capacity [ Pobierz caÅ‚ość w formacie PDF ]