Due to anthropogenic activities, heavy metals still represent a threat for various trophic levels. If aquatic animals are exposed to heavy metals we can obviously observe considerable toxicity. It is well known that an organism affected by cadmium (Cd) synthesize low molecular mass thiol compounds rich in cysteine (Cys), such as metallothioneins (MT) and glutathione (GSH/GSSG). The aim of this study was to summarize the effect of Cd on level of thiol compounds in aquatic organisms, and evaluate that the concentrations of thiol compounds are effective indicators of Cd water pollution and explain their potential use in biomonitoring applications.

University of Veterinary and Pharmaceutical Sciences Brno Faculty of Veterinary Hygiene and Ecology Department of Veterinary Public Health and Toxicology 612 42 Brno Czech Republic

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Alvarado NE, Buxens A, Mazón LI, Marigómez I, Soto M. Cellular biomarkers of exposure and biological effect in hepatocytes of turbot (Scophthalmus maximus) exposed to Cd, Cu and Zn and after depuration. Aquat Toxicol. 2005;74:110–125. PubMed

Alvarado NE, Quesada I, Hylland K, Marigomez I, Soto M. Quantitative changes in metallothionein expression in target cell-types in the gills in turbot (Scophthalamus maximus) exposed to Cd, Cu, Zn and after a depuration treatment. Aquat Toxicol. 2006;77:64–77. PubMed

Amiard JC, Amiard-Triquet C, Barka S, Pellerin J, Rainbow PS. Metallothioneins in aquatic invertebrates. Their role in metal detoxification and their use as biomarkers. Aquat Toxicol. 2006;76:160–202. PubMed

Bae H, Nam SS, Park H-S, Park K. Metallothionein mRNA sequencing and induction by cadmium in gills of the crucian carp (Carassius auratus) J Health Sci. 2005;51:284–290.

Baer KN, Thomas P. Influence of capture stress, salinity, and reproductive status on zinc associated with metallothionein-like proteins in livers of three marine teleost species. Mar Environ Res. 1990;29:277–287.

Belcastro M, Marino T, Russo N, Toscano M. The role of glutathione in cadmium ion detoxification: Coordination modes and binding properties – A density functional study. J Inorg Biochem. 2009;103:50–57. PubMed

Berntssen MHG, Aspholm OO, Hylland K, Bonga SEW, Lundebye AK. Tissue metallothionein, apoptosis and cell proliferation responses in Atlantic salmon (Salmo salar L.) parr fed elevated dietary cadmium. Comp Bioch Phys. 2001;128:299–310. PubMed

Bervoets L, Blust R. Metal concentrations in water, sediment and gudgeon (Gobio gobio) from a pollution gradient: relationship with fish condition factor. Environ Pollut. 2003;126:9–19. PubMed

Blahova J, Kruzikova K, Hilscherova K, Grabic R, Halirova J, Jurcikova J, Ocelka T, Svobodova Z. Biliary 1-hydroxypyrene as a biomarker of exposure to polycyclic aromatic hydrocarbons in fish. Neuroendocrinol Lett. 2008;29:663–668. PubMed

Bonwick GA, Fielden PR, Davies DH. Hepatic metallothionein levels in roach (Rutilus rutilus L.) continuously exposed to water-borne cadmium. Comp Biochem Physiol. 1991;99C:119–125.

Bouraoui Z, Banni M, Ghedira J, Clerandeau C, Guerbej H, Narbonne JF, Boussetta H. Acute effects of cadmium on liver phase I and phase II enzymes and metallothionein accumulation on sea bream Sparus aurata . Fish Physiol Biochem. 2008;34:201–207. PubMed

Brouwer M, Schlenk D, Ringwood AH, Brouwer-Hoexum TM. Metal-specific induction of metallothionein isoforms in the blue crab Callinectes sapidus in response to single- and mixed-metal exposure. Arch Biochem Biophys. 1992;294:461. PubMed

Cajaraville MP, Abascal I, Etxeberria M, Marigómez I. Lysosomes as cellular markers of environmental pollution: time and dose-dependent responses of the digestive lysosomal system of mussels after petroleum hydrocarbon exposure. Environ Toxicol Water Qual. 1995;10:1–8.

Chatterjee S, Bhattacharya S. Detoxification of industrial pollutants by the glutathione and glutathione-S-transferase system in the liver of Anabas testudineus (Bloch) Toxicol Lett. 1984;22:187–193. PubMed

Correia AD, Lima G, Costa MH, Livingstone DR. Studies on biomarkers of copper exposure and toxicity in the marine amphipod Gammarus locusta (crustacean) Biomarkers. 2002;7:422–437. PubMed

Coyle P, Philcox JC, Carey LC, Rofe AM. Metallothionein: the multipurpose protein. Cell Mol Life Sci. 2002;59:627–647. PubMed PMC

Dallinger R. Mechanisms of metal incorporation into cells. In: Cajaraville MP, editor. Cell Biology in Environmental toxicology. Bilbao: University of Basque Country Press Service; 1995. pp. 133–154.

Dallinger R, Egg M, Köck G, Hofer R. The role of metallothionein in cadmium accumulation of Arctic char (Salvelinus alpinus) from high alpine lakes. Aquat Toxicol. 1996;38:47–66.

De Boeck G, Ngo TT, Van Campenhout K, Blust R. Differential metallothionein induction patterns in three freshwater fish during sublethal copper exposure. Aquat Toxicol. 2003;65:413–424. PubMed

De Smet H, De Wachter B, Lobinski R, Blust R. Dynamics of (Cd, Zn)-metallothioneins in gills, liver and kidney of common carp (Cyprinus carpio) during cadmium exposure. Aquat Toxicol. 2001;52:269–281. PubMed

Depledge MH. The rational basis for the use of biomarkers as ecotoxicological tools. In: Fossi MC, Leonzio C, editors. Non-destructive biomarkers in vertebrates. Boca Raton: Lewis Publishers; 1993. pp. 261–285.

Eaton DL, Stacey NH, Wong KL, Klaassen CD. Dose-response effects of various metal ions on rat liver, metallothionein, glutathione, heme oxygenase and cytochrome P-450. Toxicol Appl Pharmacol. 1980;55:393–402. PubMed

Ferreira M, Caetano M, Costa J, Pousao-Ferreira P, Vale C, Reis-Henriques MA. Metal accumulation and oxidative stress responses in, cultured and wild, white seabream from Northwest Atlantic. Sci Total Environ. 2008;407:638–646. PubMed

Foulkes EC. Metallothionein and glutathione as determinants of cellular retention and extrusion of cadmium and mercury. Life Sci. 1993;52:1611–1620. PubMed

Fowler BA, Hildebrand CE, Kojima Y, Webb M. Nomenclature of metallothionein. In: Kagi JHR, Kojima Y, editors. Metallothionein II. Basel: Birkhauser-Verlag; 1987. pp. 19–22. PubMed

Friberg L, Kjellström T, Nordberg GF. Cadmium. In: Friberg L, Nordberg GF, Vouk VB, editors. Handbook on the toxicology of metals, vol II. Specific metals. Amsterdam: Elsevier; 1986. pp. 130–184.

Glynn AW, Olsson P-E. Cadmium turnover in minnows (Phoxinus phoxinus) pre-exposed to waterborne cadmium. Environ Toxicol Chem. 1991;10:383–394.

Gravato C, Teles M, Oliveira M, Santos MA. Oxidative stress, liver biotransformation and genotoxic effect induced by copper in Anguilla anguilla L. – the influence of pre-exposure of [beta]-naphtoflavone. Chemosphere. 2006;65:1821–30. PubMed

Haines TA. Acid precipitation and its consequences for aquatic ecosystems. A review. Transact Am Fish Soc. 1981;110:669–705.

Hamer DH. Metallothionein. Annu Rev Biochem. 1986;55:913–951. PubMed

Hamilton SJ, Mehrle PM, Jones JR. Evaluation of metallothionein measurement as a biological indicator of stress from cadmium to brook trout. Trans Am Fish Soc. 1987;116:551–560.

Handy RD, Eddy FB. The interaction between the surface of rainbow trout Oncorhynchus mykiss, and water-borne metal toxicants. Funct Ecol. 1990;4:385–392.

Havelkova M, Blahova J, Kroupova H, Randak T, Slatinska I, Leontovycova D, Grabic R, Pospisil R, Svobodova Z. Biomarkers of contaminant exposure in Chub (Leuciscus cephalus L.) – Biomonitoring of major rivers in the Czech Republic. Sensors. 2008;8:2589–2603. PubMed PMC

Hollis LM, McGeer JC, McDonald DG, Wood CM. Cadmium accumulation, gill Cd binding, acclimation and physiological effects during long term sublethal Cd exposure in rainbow trout. Aquat Toxicol. 1999;46:101–119.

Huang PC. Metallothionein structure/function interface. In: Sizuki KT, Imura N, Kimura M, editors. Metallothionein III: Biological Roles and Medical Implications. Basel: Birkhauser Verlag; 1993. pp. 407–426.

Huang Z-Y, Zhang Q, Chen J, Zhuang Z-X, Wang X-R. Bioaccumulation of metals and induction of metallothioneins in selected tissues of common carp (Cyprinus carpio L.) co-exposed to cadmium, mercury and lead. Appl Organometal Chem. 2007;21:101–107.

Hylland K, haux C, Hogstrand C. Immunological characterization of metallothionein in marine and freshwater fish. Res Mar Org Poll Pri. 1992;39:111–115.

Jezierska B, Witeska M. Metal toxicity to fish. Siedlce: University of Podlasie; 2001. p. 318.

Kägi JHR, Schäffer A. Biochemistry of metallothionein. Biochemistry. 1988;27:8509–8515. PubMed

Kang YJ, Clapper JA, Enger MD. Enhanced cadmium cytotoxicity in A549 cells with reduced glutathione levels is due to neither enhanced cadmium accumulation nor reduced metallothionein synthesis. Cell. Biol Toxicol. 1989;5:249–260. PubMed

Kito H, Tazawa T, Ose Y, Sato T, Ishikawa T. Formation of metallothionein in fish. Comp Biochem Physiol. 1982a;73:129–134. PubMed

Kito H, Tazawa T, Ose Y, Sato T, Ishikawa T. Protection of metallothionein against cadmium toxicity. Comp Biochem Physiol C-Pharmacol Toxicol Endocrinol. 1982b;73:135–139. PubMed

Klassen CD, Liu J, Choundry S. Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmaco Toxicol. 1999;39:267–294. PubMed

Klaverkamp JF, Duncan DA. Acclimation to cadmium toxicity by white suckers: cadmium binding capacity and metal distribution in gill and liver cytosol. Environ Toxicol Chem. 1987;6:275–289.

Köck G, Triendl M, Hofer R. Seasonal patterns of metal accumulation in Arctic char (Salvelinus alpinus) from an oligotrophic Alpine lake related to temperature. Can J Fish Aquat Sci. 1996;53:780–786.

Köhler A, Deisemanmn H, Lauritzen B. Histological and cytochemical indices of toxic injury in the liver of dab (Limanda limanda) Mar Ecol Prog Ser. 1992;91:141–153.

Kovarova J, Kizek R, Adam V, Harustiakova D, Celechovska O, Svobodova Z. Effect of cadmium chloride on metallothionein levels in carp. Sensors. 2009;9:4789–4803. PubMed PMC

Kuroshima R. Comparison of cadmium accumulation in tissues between carp (Cyprinus carpio) and red bream (Pagrus major) Nippon Suisan Gakk. 1992;58:1237–1242.

Kuroshima R. Hepatic metallothionein and glutathione levels in red sea bram. Comp Biochem Physiol. 1995;110C:95–100.

Lange A, Ausseil O, Segner H. Alterations of tissue glutathione levels and metallothionein mRNA in rainbow trout during single and combined exposure to cadmium and zinc. Comp Bioch Physiol. 2002;131:231–243. PubMed

Lecoeur S, Videman B, Berny P. Evaluation of metallothionein as a biomarker of single and combined Cd/Cu exposure in Dresseina polymorpha. Environ Res. 2004;94:184–191. PubMed

Lowe DM, Moore MN, Clarke KR. Effects of oil on digestive cells in mussels: quantitative alterations in cellular and lysosomal structure. Aquat Toxicol. 1981;1:213–226.

Maracine M, Segner H. Cytotoxicity of metals in isolated fish cells: Importance of the cellular glutathione status. Compar Biochem Physiol. 1998;120A:83–88.

Marigomez I, Soto M, Carajaville MP, Angulo E, Giamberini L. Cellular and subcellular distribution of metals in molluscs. Microsc Res Technol. 2002;56:358–392. PubMed

Martín -Díaz ML, Blasco J, Sales D, Delvalls TA. Biomarkers study for sediment quality assessment in spanish ports using the crab Carcinus maenas and the clam Ruditapes phillippinarum . Environ Contam Toxicol. 2007;53:66–76. PubMed

Mason AZ, Jenkins KD. Metal detoxification in aquatic organisms. In: Tessier A, Turner DR, editors. Metal Speciation and Bioavailability in Aquatic Ecosystems. New York, NY: Wiley; 1995. pp. 478–608.

Mathiessen P. Biological effects quality assurance in monitoring programs (BELQUALM); Remenbrance Avenue, Burham-on-Crouch, Essex CMO 8HA, UK. Centre for Environment, Fisheries and Aquaculture Science (CEFAS); 2000. p. 24.

McCarthy JF, Shugard LR. Biological markers of environmental contamination. In: McCarthy JF, Stuart LR, editors. Biomarkers of Environmental Contamination. Boca Raton, Florida: Lewis Publishers; 1990. pp. 3–14.

McDonald DG, Wood CM. Branchial mechanisms of acclimation to metals in freshwater fish. In: Rankin JC, Jensen JB, editors. Fish Ecophysiology. London: Chapmann & Hall; 1993. pp. 297–315.

McGeer JC, Szebedinszky C, McDonald DG, Wood CM. Effects of chronic sublethal exposure to waterborne Cu, Cd or Zn in rainbow trout 2: tissue specific metal accumulation. Aquat Toxicol. 2000;50:245–256. PubMed

McGeer JC, Nadella S, Alsop DH, Hollis L, Taylor LN, McDonald DG, Wood CM. Influence of acclimation and cross-acclimation of metals on acute Cd toxicity and Cd uptake and distribution in rainbow trout (Oncorhynchus mykiss) Aquat Toxicol. 2007;84:190–197. PubMed

Meister A, Anderson ME. Glutathione. Annu Rev Biochem. 1983;52:711–760. PubMed

Meister A. The fall and rise of cellular glutathione levels: Enzyme based approaches. Curr Top Cell Regul. 1985;26:383–394. PubMed

Norey CG, Brown MW, Cryer A, Kay J. A comparison of accumulation, tissue distribution and secretion of cadmium in the different species of freshwater fish. Comp Biochem Physiol. 1990;97C:215–220.

Olsson PE, Larsson A, Maage A. Induction of metallothionein synthesis in rainbow trout (Salmo gairdneri), during long-term exposure to waterborne cadmium. Fish Physiol Biochem. 1989;6:221–229. PubMed

Olsson PE, Kling P, Hogstrand C. Mechanisms of heavy metal accumulation of toxicity in fish. In: Langston WJ, Bebianno MJ, editors. Metal Metabolism in Aquatic Environments. London, UK: Chapman and Hall; 1998. pp. 321–350.

Olsvik PA, Gundersen P, Andersen RA, Zachariassen KE. Metal accumulation and metallothionein in two populations of brown trout (Salmo trutta), exposed to different natural water environments during a run-off episode. Aquat Toxicol. 2000;50:301–316. PubMed

Pan L, Zhang H. Metallothionein, antioxidant enzymes and DNA strand breaks as biomarkers of Cd exposure in a marine crab, Charybdis japonica . Comp Biochem Physiol. 2006;144:67–75. PubMed

Randak T, Zlabek V, Pulkrabova J, Kolarova J, Kroupova H, Siroka Z, Velisek J, Svobodova Z, Hajslova J. Effect of pollution on chub in the River Elbe, Czech Republic. Ecotoxicol Environ Saf. 2009;72:737–746. PubMed

Redeker ES, van Campenhout K, Bervoets L, Reijinders H, Blust R. Subcellular distribution of Cd in aquatic oligochaete Tubifex tubifex, implication for trophic availability and toxicity. Environ Pollut. 2006;148:166–175. PubMed

Reed DJ. Glutathione: Toxicological implications. Annu Rev Toxicol Pharmacol. 1990;30:603–631. PubMed

Roesjadi G. Metallothionein in metal regulation and toxicity in aquatic animals. Aquat Toxicol. 1992;22:81–114.

Roesijadi G. Metallothionein and its role in toxic metal regulation. Comp Biochem Physiol. 1996;113C:117–123.

Rose WL, Nisbet RM, Green PG, Norris S, Fan T, Smith EH, Cherr GN, Anderson SL. Using an integrated approach to link biomarker responses and physiological stress to growth impairment of cadmium-exposed larval topsmelt. Aquat Toxicol. 2006;80:298–308. PubMed

Santovito G, Irato P, Piccinni E, Albergoni V. Relationship between metallothionein and metal contants in red-blooded and white-blooded Antarctic teleost. Polar Biol. 2000;23:383–391.

Sarkar A, Ray D, Shrivastava AN, Sarker S. Molecular biomarkers: their significance and application in marine pollution monitoring. Ecotox. 2006;15:333–340. PubMed

Schlenk D, Rice CD. Effect of zinc and cadmium treatment on hydrogen-peroxide induced mortality and expression of glutathione and metallothionein in a teleost hepatoma cell line. Aquat Toxicol. 1998;43:121–129.

Singhal RK, Anderson ME, Meister A. Glutathione, a first line defence against cadmium toxicity. FASEB. 1987;1:220–223. PubMed

Smirnov LP, Sukhovskaya IV, Nemova NN. Effects of environmental factors on low-molecular-weight peptides of fishes. A Review Russ J Ecol. 2004;36:41–47.

Spry Dj, Wiener JG. Metal bioavailability and toxicity to fish in low-alkalinity lakes: a critical review. Environ Pollut. 1991;71:243–304. PubMed

Stacey NH, Klaassen CD. Comparison of the effects of metals on cellular injury and lipid peroxidation in isolated rat hepatocytes. J Toxicol Environ Health. 1981;7:139–147. PubMed

Stephensen E, Sturve J, Forlin L. Effects of redox cycling compounds on glutathione content and activity of glutathione-related enzymes in rainbow trout liver. Comp Biochem Physiol. 2002;133:435–442. PubMed

Sugiyama M. Role of cellular antioxidants in metal-induced damage. Cell Biol Toxicol. 1994;10:1–22. PubMed

Suzuki KT, Imura N, Kimura M. Metallothionein III. Basel: Birkhäuser; 1993. p. 479.

Szebedinszky C, McGeer JC, McDonald DM, Wood CM. Effect of chronic cadmium exposure via the diet or water on internal organ-specific distribution and subsequent gill Cd uptake kinetics in juvenile rainbow trout (Oncorhyncus mykiss) Environ Toxicol Chem. 2001;20:597–607. PubMed

Thomas P, Wofford HW, Neff JM. Effect of cadmium on glutathione content of mullet (Mugil cephalus) tissue. In: Vernberg WB, Calabrese A, Thurberg FB, Vernberg FJ, editors. Physiological mechanisms of Marine Pollutant Toxicity. NY: Academic Press; 1982. pp. 109–125.

Thomas P, Wofford HW. Effect of cadmium and arochlor 1254 on lipid peroxidation, glutathione peroxidase activity, and selected antioxidants in atlantic croaker tissues. Aquat Toxicol. 1993;27:159–178.

Tom M, Auslander M. Transcript and protein environmental biomarkers in fish – a review. Chemosphere. 2005;59:155–162. PubMed

Tort L, Kargacin B, Torres P, Giralt M, Hidalgo J. The effect of cadmium exposure and stress on plasma cortisol, metallothionein levels and oxidative status in rainbow trout (Oncorhynchus mykiss) liver. Comp Bioch Physiol. 1996;114C:29–34.

Vasak M. Riodan JF, Vallee BL, editors. Metal removal and substitution in vertebrate and invertebrate metallothioneins. Methods in enzymology metallochemistry. 1991;205:452–457. PubMed

Wiclung A, Runn P. Calcium effects on cadmium uptake, redistribution and elimination in minnows (Phoxinus phoxinus) acclimated to different calcium concentrations. Aquat Toxicol. 1988;13:109–122.

Winston DW, Di Giulio RT. Prooxidant and antioxidant mechanisms in aquatic organisms. Aquat Toxicol. 1991;19:137–161.

Wögrath S, Psenner R. Seasonal, annual and long-term variability in the water chemistry of a remote high alpine lake: acid rain versus natural changes. Wat Air Soil Pollut. 1995;85:359–364.

Won E-J, Raissudin S, Shin K-H. Evaluation of induction of metallothionein-like proteins (MTLPs) in the polychaetes for biomonitoring of heavy metal pollution in marine sediments. Mar Pollut Bull. 2008;57:544–551. PubMed

Woo S, Yum S, Jung JH, Shim WJ, Lee Ch-H, Lee T-K. Heavy metal-induced differential gene expression of metalothionein in Javanese medaka, Oryzias javanicus. Mar Biotech. 2006;8:654–662. PubMed

Yudkovski Y, Rogowska-Wrzesinska A, Yankelevich I, Shefer E, Herut B, Tom M. Quantitative immunochemical evaluation of fish metallothionein upon exposure to cadmium. Mar Environ Res. 2008;65:427–436. PubMed

Zorita I, Apraiz I, Ortiz-Zarragoitia M, Orbea A, Cancio I, Soto M, Marigómez I, Cajaraville MP. Assessment of biological effects of environmental pollution along the NW Mediterranean sea using mussels as sentinel organisms. Environ Pollut. 2007;148:236–250. PubMed

Biochemical markers of contamination in fish toxicity tests