Mechanisms of cadmium toxicity in terrestrial pulmonates: Programmed cell death and metallothionein overload

Abstract

A sublethal dose of cadmium (Cd2+) administered via the diet during short-term exposure over 10 d induced programmed cell death in the hepatopancreas of the terrestrial pulmonate snail Helix pomatia. Condensed cell residues were predominantly phagocytosed by calcium cells, suggesting a specific function of these epithelial cells in metal detoxification or in clearing the organ of cellular debris from cell death. The considerable cell loss recorded by histological analysis was accompanied by enhanced cell proliferation. Intoxication with Cd was further associated with the pronounced abundance of residual bodies, predominantly recorded in excretory cells, and with pathological changes in the endoplasmic reticulum. During long-term Cd exposure, mortality increased with increasing Cd concentrations in the diet, as demonstrated by feeding experiments in the laboratory. Lethal effects of Cd appeared to be correlated with Cd overloading of the Cd-specific metallothionein isoform (Cd-MT), isolated and characterized previously from the animal's hepatopancreas. Stoichiometric analysis shows that the capacity of Cd-MT to bind six molar equivalents of Cd corresponds to a tissue Cd concentration of approximately 4 micromol/g dry weight. At this tissue concentration, all high-affinity metal-binding sites of Cd-MT are occupied by Cd2+. Cadmium exposure beyond this level gives rise to progressive destabilization of Cd-MT cluster structure in vitro, resulting in increasing proportions of weakly bound, or even unbound, Cd2+ ions. Our results suggest that in vivo, the observed overburdening of Cd-MT with Cd2+ reduces the viability of affected animals.

Bioaccumulation and histopathological changes of the digestive gland of the land snailEobania vermiculata(Mollusca: Gastropoda), as biomarkers of terrestrial heavy metal pollution in Taif city

“…These results agreed with the findings of Chabicovsky et al (2004) who showed that heavy metal pollutants, such as Cd, Cu and Zn, induce an increased number of excretory cells of the digestive gland. The current results also were in agreement with the findings of Hamed et al (2007), who found that methomyl-treatment increased the number and size of excretory granules after 5 and 7 days of topical application to E. vermiculata.…”

Cadmium stress stimulates tissue turnover in Helix pomatia: increasing cell proliferation from metal tolerance to exhaustion in molluscan midgut gland

“…The observation that, for Cdexposed individuals of the gray garden slug, D. reticulatum, similar patterns and threshold levels (referred to Cd concentrations in the food) have been described by Triebskorn and Köhler (1996) is therefore of interest. Increased individual mortality, as seen previously for H. pomatia in a long-term exposure study with Cd concentrations similar to those applied in the present study (see Chabicovsky et al 2004), is a necessary corollary of such processes of cellular deterioration.…”

“…Additional to enhanced ER, intensification of electron-dense structures in basophilic cell granules after Cd exposure, as demonstrated in the present study (see Fig. 5b, d), can be interpreted as the enhanced accumulation of acid mucopolysaccharides (Gupta 1977;Chabicovsky et al 2004) and might also be regarded as an indication of increased cellular turnover upon stress impact.…”

“…Palacios, A. Pagani, S. Pérez-Rafael, M. Egg, M. Höckner, D. Schuler, M. Capdevila, S. Atrian, R. Dallinger, in preparation). Cd 2+ exposure in these animals also induces cellular alterations and programmed cell death Chabicovsky et al 2004;Zaldibar et al 2008). In contrast to the MT defense strategy, cellular alterations attributable to metal intoxication are more difficult to interpret (Dallinger et al 2001a;Knigge et al 2002), and the interplay between MT detoxification and cellular responses is not yet completely understood.…”

Histopathological Changes Induced by Metaldehyde in Eobania vermiculata (Müller 1774)

“…However, digestive and excretory cells have been observed in E. vermiculata (Al-Zahaby et al, 1993). Most findings are consistent with the hypothesis that the digestive gland epithelium of terrestrial gastropods is composed of three cell types: digestive cells, calcium cells and excretory cells (Babua and SkowronskWendland, 1988;Mersal, 1990;Aioub et al, 2000;Dimitriadis, 2001;Chabicovsky et al 2004 andSnyman et al, 2005). The presence of fourth type, the thin cells, have been documented in H. aspersa, A. reticulatus and E. vermiculata (Sumner, 1965(Sumner, , 1969Walker, 1970;Beshr, 2000 andHamed et al, 2007).…”