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Environmental Science and Pollution Research

, Volume 23, Issue 2, pp 1664–1670 | Cite as

Vitamin C modulates cadmium-induced hepatic antioxidants’ gene transcripts and toxicopathic changes in Nile tilapia, Oreochromis niloticus

  • Yasser S. El-Sayed
  • Ahmed M. El-Gazzar
  • Abeer F. El-Nahas
  • Khaled M. Ashry
Research Article

Abstract

Cadmium (Cd) is one of the naturally occurring heavy metals having adverse effects, while vitamin C (l-ascorbic acid) is an essential micronutrient for fish, which can attenuate tissue damage owing to its chain-breaking antioxidant and free radical scavenger properties. The adult Nile tilapia fish were exposed to Cd at 5 mg/l with and without vitamin C (500 mg/kg diet) for 45 days in addition to negative and positive controls fed with the basal diet and basal diet supplemented with vitamin C, respectively. Hepatic relative mRNA expression of genes involved in antioxidant function, metallothionein (MT), glutathione S-transferase (GST-α1), and glutathione peroxidase (GPx1), was assessed using real-time reverse transcription polymerase chain reaction (RT-PCR). Hepatic architecture was also histopathologically examined. Tilapia exposed to Cd exhibited upregulated antioxidants’ gene transcript levels, GST-⍺1, GPx1, and MT by 6.10-, 4.60-, and 4.29-fold, respectively. Histopathologically, Cd caused severe hepatic changes of multifocal hepatocellular and pancreatic acinar necrosis, and lytic hepatocytes infiltrated with eosinophilic granular cells. Co-treatment of Cd-exposed fish with vitamin C overexpressed antioxidant enzyme-related genes, GST-⍺1 (16.26-fold) and GPx1 (18.68-fold), and maintained the expression of MT gene close to control (1.07-fold), averting the toxicopathic lesions induced by Cd. These results suggested that vitamin C has the potential to protect Nile tilapia from Cd hepatotoxicity via sustaining hepatic antioxidants’ genes transcripts and normal histoarchitecture.

Keywords

Cadmium Vitamin C Hepatotoxicity Antioxidants Gene expression RT-PCR 

References

  1. Abd El-Gawad EA, Abdel Hamid OM (2014) Effect of vitamin C dietary supplementation in reducing the alterations induced by fenitrothion in Oreochromis niloticus. Fish Physiol Biochem 40:787–96. doi: 10.1007/s10695-013-9885-4 CrossRefGoogle Scholar
  2. Abdel-Moneim AM, Al-Kahtani MA, Elmenshawy OM (2012) Histopathological biomarkers in gills and liver of Oreochromis niloticus from polluted wetland environments, Saudi Arabia. Chemosphere 88:1028–35. doi: 10.1016/j.chemosphere.2012.04.001 CrossRefGoogle Scholar
  3. AbdEl-Rahim WM, Khalil WKB, Eshak MG (2010) Evaluation of the gene expression changes in Nile tilapia (Oreochromis niloticus) as affected by the bio-removal of toxic textile dyes from aqueous solution in small-scale bioreactor. Environmentalist 30:242–253. doi: 10.1007/s10669-010-9268-7 CrossRefGoogle Scholar
  4. Alhama J, Romero-Ruiz A, Lopez-Barea J (2006) Metallothionein quantification in clams by reversed-phase high-performance liquid chromatography coupled to fluorescence detection after monobromobimane derivatization. J Chromatogr A 1107:52–8. doi: 10.1016/j.chroma.2005.11.057 CrossRefGoogle Scholar
  5. Amiard JC, Cosson RP (1997) Les métallothionéines. In: Lagadic L, Caquet T, Amiard JC, Ramade F (eds) Biomarqueurs en écotoxicologie: aspects fondamentaux. Masson, Masson, Paris, pp 53–66Google Scholar
  6. Baillon L, Pierron F, Coudret R, Normendeau E, Caron A, Peluhet L, Labadie P, Budzinski H, Durrieu G, Sarraco J, Elie P, Couture P, Baudrimont M, Bernatchez L (2015) Transcriptome profile analysis reveals specific signatures of pollutants in Atlantic eels. Ecotoxicology 24:71–84. doi: 10.1007/s10646-014-1356-x CrossRefGoogle Scholar
  7. Bancroft D, Stevens A, Turner R (1996) Theory and practice of histological techniques. Churchill living stone, Edinburg, London, MelbourneGoogle Scholar
  8. Basha PS, Rani AU (2003) Cadmium-induced antioxidant defense mechanism in freshwater teleost Oreochromis mossambicus (tilapia). Ecotoxicol Environ Saf 56:218–21. doi: 10.1016/S0147-6513(03)00028-9 CrossRefGoogle Scholar
  9. Casalino E, Calzaretti G, Landriscina M, Sblano C, Fabiano A, Landriscina C (2007) The Nrf2 transcription factor contributes to the induction of alpha-class GST isoenzymes in liver of acute cadmium or manganese intoxicated rats: comparison with the toxic effect on NAD(P)H:quinone reductase. Toxicology 237:24–34. doi: 10.1016/j.tox.2007.04.020 CrossRefGoogle Scholar
  10. Cheung AP, Lam TH, Chan KM (2004) Regulation of tilapia metallothionein gene expression by heavy metal ions. Mar Environ Res 58:389–94. doi: 10.1016/j.marenvres.2004.03.084 CrossRefGoogle Scholar
  11. Choi CY, An KW, Nelson ER, Habibi HR (2007) Cadmium affects the expression of metallothionein (MT) and glutathione peroxidase (GPx) mRNA in goldfish, Carassius auratus. Comp Biochem Physiol C Toxicol Pharmacol 145:595–600. doi: 10.1016/j.cbpc.2007.02.007 CrossRefGoogle Scholar
  12. Di Giulio RT, Meyer JN (2008) Reactive oxygen species and oxidative stress. In: Di Giulio RT, Hinton DE (eds) The toxicology of fishes. CRC Press, Taylor & Francis Group, New York, USA, pp 274–324CrossRefGoogle Scholar
  13. Durou C, Smith BD, Romeo M, Rainbow PS, Mouneyrac C, Mouloud M, Gnassia-Barelli M, Gillet P, Deutch B, Amiard-Triquet C (2007) From biomarkers to population responses in Nereis diversicolor: assessment of stress in estuarine ecosystems. Ecotoxicol Environ Saf 66:402–11. doi: 10.1016/j.ecoenv.2006.02.016 CrossRefGoogle Scholar
  14. Eissa BL, Ossana NA, Ferrari L, Salibian A (2010) Quantitative behavioral parameters as toxicity biomarkers: fish responses to waterborne cadmium. Arch Environ Contam Toxicol 58:1032–9. doi: 10.1007/s00244-009-9434-4 CrossRefGoogle Scholar
  15. El-Gazzar AM, Ashry KE, El-Sayed YS (2014) Physiological and oxidative stress biomarkers in the freshwater Nile Tilapia, Oreochromis niloticus L., exposed to sublethal doses of cadmium. AJVS 40:29–43. doi: 10.5455/ajvs.48333 CrossRefGoogle Scholar
  16. El-Neweshy MS, El-Maddawy ZK, El-Sayed YS (2013) Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on cadmium-induced testicular toxicity. Andrologia 45:369–78. doi: 10.1111/and.12025 CrossRefGoogle Scholar
  17. El-Sokkary GH (2008) Melatonin and vitamin C administration ameliorate diazepam-induced oxidative stress and cell proliferation in the liver of rats. Cell Prolif 41:168–76. doi: 10.1111/j.1365-2184.2007.00503.x CrossRefGoogle Scholar
  18. Gayet J-C, Haouz A, Geloso-Meyer A, Burstein C (1993) Detection of heavy metal salts with biosensors built with an oxygen electrode coupled to various immobilized oxidases and dehydrogenases. Biosens Bioelectron 8:177–183. doi: 10.1016/0956-5663(93)85030-R CrossRefGoogle Scholar
  19. George S, Hodgson P, Todd K, Tytler P (1996) Metallothionein protects against cadmium toxicity—proof from studies developing turbot larvae. Mar Environ Res 42:52. doi: 10.1016/0141-1136(96)87042-5 CrossRefGoogle Scholar
  20. Gren A, Barbasz A, Kreczmer B, Sieprawska A, Rudolphi-Skorska E, Filek M (2012) Protective effect of ascorbic acid after single and repetitive administration of cadmium in Swiss mice. Toxicol Mech Methods 22:597–604. doi: 10.3109/15376516.2012.704957 CrossRefGoogle Scholar
  21. Grosicki A (2004) Influence of vitamin C on cadmium absorption and distribution in rats. J Trace Elem Med Biol 18:183–7. doi: 10.1016/j.jtemb.2004.06.003 CrossRefGoogle Scholar
  22. Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88. doi: 10.1146/annurev.pharmtox.45.120403.095857 CrossRefGoogle Scholar
  23. He X, Chen MG, Ma Q (2008) Activation of Nrf2 in defense against cadmium-induced oxidative stress. Chem Res Toxicol 21:1375–83. doi: 10.1021/tx800019a CrossRefGoogle Scholar
  24. Hoarau P, Damiens G, Romeo M, Gnassia-Barelli M, Bebianno MJ (2006) Cloning and expression of a GST-pi gene in Mytilus galloprovincialis. Attempt to use the GST-pi transcript as a biomarker of pollution. Comp Biochem Physiol C Toxicol Pharmacol 143:196–203. doi: 10.1016/j.cbpc.2006.02.007 CrossRefGoogle Scholar
  25. Hollis L, Hogstrand C, Wood CM (2001) Tissue-specific cadmium accumulation, metallothionein induction, and tissue zinc and copper levels during chronic sublethal cadmium exposure in juvenile rainbow trout. Arch Environ Contam Toxicol 41:468–74. doi: 10.1007/s002440010273 CrossRefGoogle Scholar
  26. Ibrahem MD, Fathi M, Mesalhy S, Abd El-Aty AM (2010) Effect of dietary supplementation of inulin and vitamin C on the growth, hematology, innate immunity, and resistance of Nile tilapia (Oreochromis niloticus). Fish Shellfish Immunol 29:241–6. doi: 10.1016/j.fsi.2010.03.004 CrossRefGoogle Scholar
  27. Jebali J, Banni M, Guerbej H, Almeida EA, Bannaoui A, Boussetta H (2006) Effects of malathion and cadmium on acetylcholinesterase activity and metallothionein levels in the fish Seriola dumerilli. Fish Physiol Biochem 32:93–8. doi: 10.1007/s10695-006-0041-2 CrossRefGoogle Scholar
  28. Jiang WD, Liu Y, Jiang J, Wu P, Feng L, Zhou XQ (2015) Copper exposure induces toxicity to the antioxidant system via the destruction of Nrf2/ARE signaling and caspase-3-regulated DNA damage in fish muscle: amelioration by myo-inositol. Aquat Toxicol 159:245–55. doi: 10.1016/j.aquatox.2014.12.020 CrossRefGoogle Scholar
  29. Jordanova M, Miteva N, Rocha E (2007) A quantitative study of the hepatic eosinophilic granule cells and rodlet cells during the breeding cycle of Ohrid trout, Salmo letnica Kar. (Teloestei, Salmonidae). Fish Shellfish Immunol 23:473–8. doi: 10.1016/j.fsi.2006.11.004 CrossRefGoogle Scholar
  30. Jun HJ, Kim S, Dawson K, Choi DW, Kim JS, Rodriguez RL, Lee SJ (2011) Effects of acute oral administration of vitamin C on the mouse liver transcriptome. J Med Food 14:181–94. doi: 10.1089/jmf.2010.1087 CrossRefGoogle Scholar
  31. Kan Y, Cengiz EI, Ugurlu P, Yanar M (2012) The protective role of vitamin E on gill and liver tissue histopathology and micronucleus frequencies in peripheral erythrocytes of Oreochromis niloticus exposed to deltamethrin. Environ Toxicol Pharmacol 34:170–9. doi: 10.1016/j.etap.2012.03.009 CrossRefGoogle Scholar
  32. Kim JH, Wang SY, Kim IC, Ki JS, Raisuddin S, Lee JS, Han KN (2008) Cloning of a river pufferfish (Takifugu obscurus) metallothionein cDNA and study of its induction profile in cadmium-exposed fish. Chemosphere 71:1251–9. doi: 10.1016/j.chemosphere.2007.11.067 CrossRefGoogle Scholar
  33. Kim JH, Dahms HU, Rhee JS, Lee YM, Lee J, Han KN, Lee JS (2010) Expression profiles of seven glutathione S-transferase (GST) genes in cadmium-exposed river pufferfish (Takifugu obscurus). Comp Biochem Physiol C Toxicol Pharmacol 151:99–106. doi: 10.1016/j.cbpc.2009.09.001 CrossRefGoogle Scholar
  34. Koyuturk M, Yanardag R, Bolkent S, Tunali S (2007) The potential role of combined anti-oxidants against cadmium toxicity on liver of rats. Toxicol Ind Health 23:393–401. doi: 10.1177/0748233707081907 CrossRefGoogle Scholar
  35. Kumar P, Prasad Y, Patra AK, Ranjan R, Swarup D, Patra RC, Pal S (2009) Ascorbic acid, garlic extract and taurine alleviate cadmium-induced oxidative stress in freshwater catfish (Clarias batrachus). Sci Total Environ 407:5024–30. doi: 10.1016/j.scitotenv.2009.05.030 CrossRefGoogle Scholar
  36. Legeay A, Achard-Joris M, Baudrimont M, Massabuau JC, Bourdineaud JP (2005) Impact of cadmium contamination and oxygenation levels on biochemical responses in the Asiatic clam Corbicula fluminea. Aquat Toxicol 74:242–53. doi: 10.1016/j.aquatox.2005.05.015 CrossRefGoogle Scholar
  37. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods 25:402–8. doi: 10.1006/meth.2001.1262 CrossRefGoogle Scholar
  38. Mahrous KF, Hassan AM, Radwan HA, Mahmoud MA (2015) Inhibition of cadmium- induced genotoxicity and histopathological changes in Nile tilapia fish by Egyptian and Tunisian montmorillonite clay. Ecotoxicol Environ Saf 119:140–7. doi: 10.1016/j.ecoenv.2015.04.054 CrossRefGoogle Scholar
  39. Martyniuk CJ, Sanchez BC, Szabo NJ, Denslow ND, Sepulveda MS (2009) Aquatic contaminants alter genes involved in neurotransmitter synthesis and gonadotropin release in largemouth bass. Aquat Toxicol 95:1–9. doi: 10.1016/j.aquatox.2009.06.009 CrossRefGoogle Scholar
  40. M’Kandawire E, Syakalima M, Muzandu K, Pandey G, Simuunza M, Nakayama SM, Kawai YK, Ikenaka Y, Ishizuka M (2012) The nucleotide sequence of metallothioneins (MT) in liver of the Kafue lechwe (Kobus leche kafuensis) and their potential as biomarkers of heavy metal pollution of the Kafue River. Gene 506:310–6. doi: 10.1016/j.gene.2012.07.002 CrossRefGoogle Scholar
  41. Mohamed OI, El-Nahas AF, El-Sayed YS, Ashry KM (2015) Ginger extract modulates Pb-induced hepatic oxidative stress and expression of antioxidant gene transcripts in rat liver. Pharm Biol 16:1–9. doi: 10.3109/13880209.2015.1057651 CrossRefGoogle Scholar
  42. Nair AR, Degheselle O, Smeets K, Van Kerkhove E, Cuypers A (2013) Cadmium-induced pathologies: where is the oxidative balance lost (or not)? Int J Mol Sci 14:6116–43. doi: 10.3390/ijms14036116 CrossRefGoogle Scholar
  43. Part P, Lock RA (1983) Diffusion of calcium, cadmium and mercury in a mucous solution from rainbow trout. Comp Biochem Physiol C 76:259–63. doi: 10.1016/0742-8413(83)90075-0 CrossRefGoogle Scholar
  44. Peters JM, Duncan JR, Wiley LM, Keen CL (1995) Influence of antioxidants on cadmium toxicity of mouse preimplantation embryos in vitro. Toxicology 99:11–8. doi: 10.1016/0300-483X(94)02989-8 CrossRefGoogle Scholar
  45. Puerto M, Gutierrez-Praena D, Prieto AI, Pichardo S, Jos A, Miguel-Carrasco JL, Vazquez CM, Camean AM (2011) Subchronic effects of cyanobacterial cells on the transcription of antioxidant enzyme genes in tilapia (Oreochromis niloticus). Ecotoxicology 20:479–90. doi: 10.1007/s10646-011-0600-x CrossRefGoogle Scholar
  46. Rhee JS, Lee YM, Hwang DS, Won EJ, Raisuddin S, Shin KH, Lee JS (2007) Molecular cloning, expression, biochemical characteristics, and biomarker potential of theta class glutathione S-transferase (GST-T) from the polychaete Neanthes succinea. Aquat Toxicol 83:104–15. doi: 10.1016/j.aquatox.2007.03.015 CrossRefGoogle Scholar
  47. Shaban El-Neweshy M, Said El-Sayed Y (2011) Influence of vitamin C supplementation on lead-induced histopathological alterations in male rats. Exp Toxicol Pathol 63:221–7. doi: 10.1016/j.etp.2009.12.003 CrossRefGoogle Scholar
  48. Sheader DL, Williams TD, Lyons BP, Chipman JK (2006) Oxidative stress response of European flounder (Platichthys flesus) to cadmium determined by a custom cDNA microarray. Mar Environ Res 62:33–44. doi: 10.1016/j.marenvres.2006.03.001 CrossRefGoogle Scholar
  49. Simmons SO, Fan CY, Yeoman K, Wakefield J, Ramabhadran R (2011) NRF2 oxidative stress induced by heavy metals is cell type dependent. Curr Chem Genomics 5:1–12. doi: 10.2174/1875397301105010001 CrossRefGoogle Scholar
  50. Tangahu BV, Sheikh Abdullah SR, Basri H, Idris M, Anuar N, Mukhlisin M (2011) A review on heavy metals (As, Pb, and Hg) uptake by plants through phytoremediation. Int J Chem Eng 2011:1–31. doi: 10.1155/2011/939161 CrossRefGoogle Scholar
  51. van Dyk JC, Pieterse GM, van Vuren JH (2007) Histological changes in the liver of Oreochromis mossambicus (Cichlidae) after exposure to cadmium and zinc. Ecotoxicol Environ Saf 66:432–40. doi: 10.1016/j.ecoenv.2005.10.012 CrossRefGoogle Scholar
  52. Webb M (1986) Role of metallothionein in cadmium metabolism. In: Foulkes E (ed) Cadmium. Handbook of experimental pharmacology. Springer Berlin, Heidelberg, pp 281–337Google Scholar
  53. Won EJ, Kim RO, Rhee JS, Park GS, Lee J, Shin KH, Lee YM, Lee JS (2011) Response of glutathione S-transferase (GST) genes to cadmium exposure in the marine pollution indicator worm, Perinereis nuntia. Comp Biochem Physiol C Toxicol Pharmacol 154:82–92. doi: 10.1016/j.cbpc.2011.03.008 CrossRefGoogle Scholar
  54. Woo S, Yum S, Park HS, Lee TK, Ryu JC (2009) Effects of heavy metals on antioxidants and stress-responsive gene expression in Javanese medaka (Oryzias javanicus). Comp Biochem Physiol C Toxicol Pharmacol 149:289–99. doi: 10.1016/j.cbpc.2008.08.002 CrossRefGoogle Scholar
  55. Yesilbudak B, Erdem C (2014) Cadmium accumulation in gill, liver, kidney and muscle tissues of common carp, Cyprinus carpio, and Nile tilapia, Oreochromis niloticus. Bull Environ Contam Toxicol 92:546–50. doi: 10.1007/s00128-014-1228-3 CrossRefGoogle Scholar
  56. You WC, Zhang L, Gail MH, Chang YS, Liu WD, Ma JL, Li JY, Jin ML, Hu YR, Yang CS, Blaser MJ, Correa P, Blot WJ, Fraumeni JF Jr, Xu GW (2000) Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors. J Natl Cancer Inst 92:1607–12CrossRefGoogle Scholar
  57. Younis E, Abdel-Warith A-W, Al-Asgah N, Ebaid H (2015) Histopathological alterations in the liver and intestine of Nile tilapia Oreochromis niloticus exposed to long-term sublethal concentrations of cadmium chloride. Chin J Oceanol Limnol 33:846–852. doi: 10.1007/s00343-015-4082-1 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary MedicineDamanhour UniversityDamanhourEgypt
  2. 2.Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary MedicineAlexandria UniversityEdfinaEgypt
  3. 3.Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary MedicineAlexandria UniversityEdfinaEgypt

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