Skip to main content
Log in

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

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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 53–66

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Bancroft D, Stevens A, Turner R (1996) Theory and practice of histological techniques. Churchill living stone, Edinburg, London, Melbourne

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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 274–324

    Chapter  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88. doi:10.1146/annurev.pharmtox.45.120403.095857

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Webb M (1986) Role of metallothionein in cadmium metabolism. In: Foulkes E (ed) Cadmium. Handbook of experimental pharmacology. Springer Berlin, Heidelberg, pp 281–337

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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 92:1607–12

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yasser S. El-Sayed.

Additional information

Responsible editor: Thomas Braunbeck

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Sayed, Y.S., El-Gazzar, A.M., El-Nahas, A.F. et al. Vitamin C modulates cadmium-induced hepatic antioxidants’ gene transcripts and toxicopathic changes in Nile tilapia, Oreochromis niloticus . Environ Sci Pollut Res 23, 1664–1670 (2016). https://doi.org/10.1007/s11356-015-5412-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-015-5412-8

Keywords

Navigation