The interplay between chemical speciation and physiology determines the bioaccumulation and toxicity of Cu(II) and Cd(II) to Caenorhabditis elegans.

Using the well-documented model organism Caenorhabditis elegans, a combined analysis of metal speciation in the exposure medium and body burdens of metals (Zn, Cu and Cd) was performed, and factors that are predictive of toxicological endpoints in single metal and mixed metal exposures were identified. Cu, and to a lesser extent Cd, is found to associate with Escherichia coli in the exposure medium (the food source for C. elegans) as evidenced by the observed decrease in both their dissolved and free metal ion concentrations. Together with a critical analysis of literature data, our results suggest that free metal ion concentrations and thus aqueous uptake routes are the best predictor of internal concentrations under all conditions considered, and of metal toxicity in single metal exposures. Additional factors are involved in determining the toxicity of metal mixtures. In general, the eventual adverse effects of metals on biota are expected to be a consequence of the interplay between chemical speciation in the exposure medium, timescale of exposure, exposure route as well as the nature and timescale of the biotic handling pathways.

Proteomics applications in Caenorhabditis elegans research.

The free-living nematode Caenorhabditis elegans is one of the most studied models in a wide variety of research fields with applications in agro- or pharmaceutical industries. It has been used for the development of new anthelminthic drugs and was proven to yield key insights in neurodegenerative diseases and metabolic syndromes. Due to its suitability for high-throughput genetic screens, efficiency for RNA interference approaches and the availability of thousands of mutants, most studies were carried out at the genetic level. However, determining the cellular function of each gene product remains an unfinished goal in this post-genomic era. A systems biology approach focusing on the actual gene products (i.e. proteins) can help unraveling this puzzle. A fundamental pillar in this research is mass spectrometry-based proteomics. We here provide an in-depth overview of proteomics-related studies in C. elegans research, with special emphasis on the methodologies and biological applications.

The combined effect of hypoxia and nutritional status on metabolic and ionoregulatory responses of common carp (Cyprinus carpio).

In the present study, the combined effects of hypoxia and nutritional status were examined in common carp (Cyprinus carpio), a relatively hypoxia tolerant cyprinid. Fish were either fed or fasted and were exposed to hypoxia (1.5-1.8mg O2L(-1)) at or slightly above their critical oxygen concentration during 1, 3 or 7days followed by a 7day recovery period. Ventilation initially increased during hypoxia, but fasted fish had lower ventilation frequencies than fed fish. In fed fish, ventilation returned to control levels during hypoxia, while in fasted fish recovery only occurred after reoxygenation. Due to this, C. carpio managed, at least in part, to maintain aerobic metabolism during hypoxia: muscle and plasma lactate levels remained relatively stable although they tended to be higher in fed fish (despite higher ventilation rates). However, during recovery, compensatory responses differed greatly between both feeding regimes: plasma lactate in fed fish increased with a simultaneous breakdown of liver glycogen indicating increased energy use, while fasted fish seemed to economize energy and recycle decreasing plasma lactate levels into increasing liver glycogen levels. Protein was used under both feeding regimes during hypoxia and subsequent recovery: protein levels reduced mainly in liver for fed fish and in muscle for fasted fish. Overall, nutritional status had a greater impact on energy reserves than the lack of oxygen with a lower hepatosomatic index and lower glycogen stores in fasted fish. Fasted fish transiently increased Na(+)/K(+)-ATPase activity under hypoxia, but in general ionoregulatory balance proved to be only slightly disturbed, showing that sufficient energy was left for ion regulation.

The effect of metal mixture composition on toxicity to C. elegans at individual and population levels.

The toxicity of zinc (Zn), copper (Cu), and cadmium (Cd) to the nematode Caenorhabditis elegans was characterised under single metal and mixture scenarios at different organisational levels. The effects on population size and body length were investigated at two concentrations corresponding to the 24 h LC5 and LC20 levels. Metal toxicity was dependent on metal concentration, exposure time and mixture composition. Populations exposed to LC20 levels of Cd, ZnCu, CuCd and ZnCuCd plummeted, while for all LC5 concentrations, population size continued to increase, albeit that single metals were less harmful than mixtures. Combinations of the LC20 concentration of Cd with a range of Zn concentrations showed concentration dependent mitigating effects on population size and antagonistic effects on mortality. By combining effects at different organisational levels, more insight into metal toxicity was obtained. Metal effects were more evident on population size than on body length or mortality, suggesting that population size could be considered as a sensitive endpoint. Furthermore, our observations of ZnCd mixture effects at the individual and population levels are consistent with literature data on the dose-dependent expression of the cdf-2 gene, which is involved in mediation of Zn and Cd toxicity.

Mixture effects of copper, cadmium, and zinc on mortality and behavior of Caenorhabditis elegans.

The toxicity effects of zinc (Zn), copper (Cu), and cadmium (Cd), both as single metals and in combination, were examined in the nematode Caenorhabditis elegans. Metal effects on lethality were analyzed in a time-dependent manner using different concentrations in K-medium. To investigate the effects on locomotion and chemosensation, lethal concentration at 20% (LC20) values were used. The results showed that Cu toxicity was higher compared with Cd and Zn, resulting in higher mortality rates and a more reduced locomotion. Lethality increased over time for all metals. When Cd was added to Cu, and vice versa, significant increases in toxicity were noted. Different interaction effects were observed for the mixtures ZnCd, ZnCu, CuCd, and ZnCuCd. Zinc seemed to have a neutral toxic effect on Cd, while in combination with Cu, a similar additive effect was seen as for the CuCd combination. Binary and tertiary metal mixtures caused a strong decrease in locomotion, except for the ZnCd combination, where Zn seemed to have a neutral effect. After LC2024 h exposure, reduced crawling speed (except for Zn) and reduced thrashing behavior (except for Zn and the ZnCd mixture) were observed. Almost no significant effects were observed on chemosensation. Because the same trend of mixture effects was noted in locomotion and in lethality tests, locomotion can probably be considered a sensitive endpoint for metal toxicities. Environ Toxicol Chem 2018;37:145-159. © 2017 SETAC.

Kidney activity increases in copper exposed goldfish (Carassius auratus auratus).

In the present study, the effect of copper was examined in the common goldfish (Carassius auratus auratus). Fish were fasted and exposed to either a high (0.84µM), a low (0.34µM) or a control copper concentration (0.05µM) for 1 and 7days. Swimming performance was not affected by either fasting or copper exposure. Food deprivation alone had no effect on ionoregulation, but low plasma osmolality levels and plasma Na+ were noticed in fasted fish exposed to Cu for 7days. Both gill Na+/K+-ATPase and H+-ATPase activities were undisturbed, while both kidney ATPase activities were up-regulated when challenged with the high Cu levels. Up-regulated kidney ATPase activities likely acted as compensatory strategy to enhance Na+ reabsorption. However, this up-regulation was not sufficient to restore Na+ to control levels in the highest exposure group.