Environmental Science and Pollution Research

, Volume 22, Issue 9, pp 6912–6919 | Cite as

Impact of acute Cd2+ exposure on the antioxidant defence systems in the skin and red blood cells of common carp (Cyprinus carpio)

Research Article


Cd2+-induced oxidative stress and its effects on the expression of stress biomarkers and on macromolecule damage in the skin and blood of common carp were studied. Both tissues play important roles in the defence mechanisms against external hazards, serving as an anatomical barrier and as connecting tissue between the organs. In the skin, the production of peroxynitrite anion and hydrogen peroxide was almost doubled after exposure to 10 mg/L Cd2+. The accumulation of these oxidant molecules suggests an intensive production of superoxide anion and nitrogen monoxide and the development of oxidative and/or nitrosative stress. Although the metallothioneins and the components of the glutathione redox system were activated in the skin, the accumulation of reactive intermediates led to the enhanced damage of lipid molecules after 24 h of metal exposure. In the blood, the basal levels of metallothionein messenger RNAs (mRNAs) were 2–2.5-fold of that measured in the skin. This high level of metallothionein expression could be the reason that the blood was less affected by an acute Cd2+ challenge and the metallothionein and glutathione systems were not activated.


Antioxidant Cadmium Erythrocyte Nitrosative stress Peroxynitrite Skin 


  1. Abdullah S, Muhammad J, Arshad J (2007) Studies on acute toxicity of metals to the fish (Labeorohita). Int J Agric Biol 9:333–337Google Scholar
  2. Ali KS, Dorgai L, Gazdag A, Abraham M, Hermesz E (2003) Identification and induction of hsp70 gene by heat shock and cadmium exposure in carp. Acta Biol Hung 54(3–4):323–334Google Scholar
  3. AMAP (1998) Assessment report: arctic pollution issues arctic monitoring and assessment programme. OsloGoogle Scholar
  4. Andrews GK (2000) Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem Pharmacol 59:95–104CrossRefGoogle Scholar
  5. Antonio MT, Corpas I, Leret ML (1999) Neurochemical changes in newborn rat’s brain after gestational cadmium and lead exposure. Toxicol Lett 104:1–9CrossRefGoogle Scholar
  6. Basha SP, Rani UA (2003) Cadmium-induced antioxidant defense mechanism in freshwater teleost Oreochromis mossambicus. Ecotoxicol Environ Saf 56:218–221CrossRefGoogle Scholar
  7. Beckman JS, Wink DA, Crow JP (1996) Nitric oxide and peroxynitrite. In: Feelisch M, Stamler J (eds) Methods in nitric oxide research. Wiley, New York, pp 61–70Google Scholar
  8. Beers RF Jr, Sizer IW (1953) Catalase assay with special reference to manometric methods. Science 117(3052):710–712CrossRefGoogle Scholar
  9. Cunha Bastos VLF, Salles JB, Valente RH, León IR, Perales J, Dantas RF, Albano RM, Bastos FF, Cunha Bastos J (2007) Cytosolic glutathione peroxidase from liver of pacu (Piaractus mesopotamicus), a hypoxia-tolerant fish of the Pantana. Biochimie 89:1332–1342CrossRefGoogle Scholar
  10. Dringen R, Gutterer JM, Hirrlinger J (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 267(16):4912–4916CrossRefGoogle Scholar
  11. Dugmonits K, Ferencz A, Jancso Z, Juhasz R, Hermesz E (2013) Major distinctions in the antioxidant responses in liver and kidney of Cd(2+)-treated common carp (Cyprinus carpio). Comp Biochem Physiol C Toxicol Pharmacol 158(4):225–230CrossRefGoogle Scholar
  12. Fridovich I (1989) Superoxide dismutases. An adaptation to a paramagnetic gas. J Biol Chem 264:7761–7764Google Scholar
  13. Fulladosa E, Deane E, Ng AH, Woo NY, Murat JC, Villaescusa I (2006) Stress proteins induced by exposure to sublethal levels of heavy metals in sea bream (Sparus sarba) blood cells. Toxicol In Vitro 20:96–100CrossRefGoogle Scholar
  14. Goyer RA, Miller CR, Zhu SY, Victery W (1989) Non-metallothionein-bound cadmium in the pathogenesis of cadmium nephrotoxicity in the rat. Toxicol Appl Pharmacol 101(2):232–244CrossRefGoogle Scholar
  15. Hallenbeck WH (1984) Human health effects of exposure to cadmium. Experientia 40:136–142CrossRefGoogle Scholar
  16. Han XY, Huang QC, Liu BJ, Xu ZR, Wang YZ (2007) Changes of porcine growth hormone and pituitary nitrogen monoxide production as a response to cadmium toxicity. Biol Trace Elem Res 119:128–136CrossRefGoogle Scholar
  17. Hansen JA, Welsh PG, Lipton J, Suedkamp MJ (2002) The effects of long-term cadmium exposure on the growth and survival of juvenile bull trout (Salvelinus confluentus). Aquat Toxicol 58:165–174CrossRefGoogle Scholar
  18. Heath AG (1995) Water pollution and fish physiology. CRC Press, Boca RatonGoogle Scholar
  19. Hermesz E, Ferencz A (2009) Identification of two phospholipid hydroperoxide glutathione peroxidase (gpx4) genes in common carp. Comp Biochem Physiol C Toxicol Pharmacol 150(1):101–106CrossRefGoogle Scholar
  20. Hermesz E, Abraham M, Nemcsok J (2001) Tissue-specific expression of two metallothionein genes in common carp during cadmium exposure and temperature shock. Comp Biochem Physiol C Toxicol Pharmacol 128(3):457–465CrossRefGoogle Scholar
  21. Huie RE, Padmaja S (1993) The reaction of NO with superoxide. Free Radic Res Commun 18(4):195–199CrossRefGoogle Scholar
  22. Imai H, Nakagawa Y (2003) Biological significance of phospholipid hydroperoxide glutathione peroxidase (PhGPx, GPx4) in mammalian cells. Free Rad Biol Med 34(2):145–169CrossRefGoogle Scholar
  23. Jancso Z, Hermesz E (2014) Impact of acute arsenic and cadmium exposure on the expression of two haeme oxygenase genes and other antioxidant markers in common carp (Cyprinus carpio). J Appl Toxicol [Epub ahead of print]Google Scholar
  24. Jezierska B, Lugowska K, Witeska M (2009) The effects of heavy metals on embryonic development of fish (a review). Fish Physiol Biochem 35(4):625–640CrossRefGoogle Scholar
  25. Karin M, Herschman HR (1980) Characterization of the metallothioneins induced in HeLa cells by dexamethasone and zinc. Eur J Biochem 107:395–401CrossRefGoogle Scholar
  26. Kito H, Ose Y, Hayashi K, Yonezawa S, Sato T, Ishikawa T, Nagase H (1984) Some properties of metallothoneins from hepatopancreas and kidney in carp (Cyprinus carpio). Eisei Kagaku 30:119–125CrossRefGoogle Scholar
  27. Kunimoto M, Miura T, Kubota K (1985) An apparent acceleration of age-related changes of rat red blood cells by cadmium. Toxicol Appl Pharmacol 77:451–457CrossRefGoogle Scholar
  28. Limaye DA, Shaikh ZA (1999) Cytotoxicity of cadmium and characteristics of its transport in cardiomyocytes. Toxicol Appl Pharmacol 154:59–66CrossRefGoogle Scholar
  29. Lowry OH, Rosebrough EA, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  30. Lü JM, Lin PH, Yao Q, Chen C (2010) Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med 14:840–860CrossRefGoogle Scholar
  31. Maiorino M, Thomas JP, Girotti AW, Ursini F (1991) Reactivity of phospholipid hydroperoxide glutathione peroxidase with membrane and lipoprotein lipid hydroperoxides. Free Radic Res Commun 12–13:131–135CrossRefGoogle Scholar
  32. Maiorino M, Aumann KD, Brigelius-Flohe R, Doria D, van den Heuvel J, McCarthy J, Roveri A, Ursini F, Flohe L (1998) Probing the presumed catalytic triad of a selenium-containing peroxidase by mutational analysis. Z Ernahrungswiss 37:118–121Google Scholar
  33. Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170–3175Google Scholar
  34. Murphy BJ, Andrews GK, Bittel D, Discher DJ, McCue J, Green CJ, Yanovsky M, Giaccia A, Sutherland RM, Laderoute KR, Webster KA (1999) Activation of metallothionein gene expression by hypoxia involves metal response elements and metal transcription factor-1. Cancer Res 59:1315–1322Google Scholar
  35. Mzimela HM, Wepener V, Cyrus DP (2003) Seasonal variation of selected metals in sediments, water and tissues of the groovy mullet, Liza dumerelii (Mugilidae) from the Mhlathuze Estuary, South Africa. Mar Pollut Bull 46(5):659–664CrossRefGoogle Scholar
  36. Nogueira CW, Quinhones EB, Jung EAC, Zeni G, Rocha JBT (2003) Anti-inflammatory and antinociceptive activity of biphenyl diselenide. Inflamm Res 52:56–63CrossRefGoogle Scholar
  37. Potter DW, Tran TB (1993) Apparent rates of glutathione turnover in rat tissues. Toxicol Appl Pharmacol 120(2):186–192CrossRefGoogle Scholar
  38. Prins JM, Fu L, Guo L, Wang Y (2014) Cd2+-induced alteration of the global proteome of human skin fibroblast cells. J Proteome Res 13(3):1677–1687CrossRefGoogle Scholar
  39. Radi R, Peluffo G, Alvarez MN, Naviliat M, Cayota A (2001) Unraveling peroxynitrite formation in biological systems. Free Rad Biol Med 30(5):463–488CrossRefGoogle Scholar
  40. Rahman I, Bel A, Mulier B, Lawson MF, Harrison DJ, Macnee W, Smith CA (1996) Transcriptional regulation of gamma-glutamylcysteine synthetase-heavy subunit by oxidants in human alveolar epithelial cells. Biochem Biophys Res Commun 229(3):832–837CrossRefGoogle Scholar
  41. Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PE, Williams DJ, Moore MR (2003) A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett 137:65–83CrossRefGoogle Scholar
  42. Schafer FQ, Buettner GR (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30:1191–1212CrossRefGoogle Scholar
  43. Sedlak J, Lindsay RH (1968) Estimation of total protein-bound and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25(1):192–205CrossRefGoogle Scholar
  44. Serbinova E, Khwaja S, Reznick AZ, Packer L (1992) Thioctic acid protects against ischemia-reperfusion injury in the isolated perfused Langendorff heart. Free Radic Res 17:49–58CrossRefGoogle Scholar
  45. Tietze F (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione. Applications to mammalian blood and other tissues. Anal Biochem 27:502–522CrossRefGoogle Scholar
  46. Tzirogiannis KN, Panoutsopoulos GI, Demonakou MD, Hereti RI, Alexandropoulou KN, Basayannis AC, Mykoniatis MG (2003) Time-course of cadmium-induced acute hepatotoxicity in the rat liver: the role of apoptosis. Arch Toxicol 77:694–701CrossRefGoogle Scholar
  47. Villegas E, Gilliland SE (1998) Hydrogen peroxide production by Lactobacillus delbrueckii Subsp. Lactis I at 5 °C. J Food Sci 63:1070–1074CrossRefGoogle Scholar
  48. Waalkes MP, Rehm S, Perantoni AO, Coogan TP (1992) Cadmium exposure in rats and tumours of the prostate. IARC Sci Publ 118:391–400Google Scholar
  49. Wang W, Ballatori N (1998) Endogenous glutathione conjugates: occurrence and biological functions. Pharmacol Rev 50:335–356Google Scholar
  50. Wang Y, Fang J, Leonard SS, Rao KM (2004) Cadmium inhibits the electron transfer chain and induces reactive oxygen species. Free Radic Biol Med 36(11):1434–1443CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Faculty of Science and InformaticsUniversity of SzegedSzegedHungary

Personalised recommendations