Skip to main content
Log in

The Protective Roles of Selenium on Hepatic Tissue Ultrastructure and Mitochondrial Antioxidant Capacity in Copper-Overloaded Rats

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The aim of this study was to explore the effects of selenium addition on hepatic tissue ultrastructure and mitochondrial antioxidant capacity in copper-overloaded rats. Eighteen adult male Sprague-Dawley (SD) rats were randomly divided into three groups (n = 6 per group). Each group received 1 mL (intragastrically) of water (control, group I) or water containing copper chloride (CuCl2, 1 mol/L) (group II) or a mixture of CuCl2 (1 mol/L) with sodium selenite (Na2SeO3, 0.05 mol/L) (group III) once daily for 30 days. Histological examination revealed normal hepatocyte structure and no ultrastructural changes in mitochondria in controls. In contrast, group II exhibited severe ultrastructural alterations, fuzzy mitochondrial membranes, irregularly shaped and fragmented rough endoplasmic reticulum (RER), and the high melanin content; group III also exhibited larger amounts of engulfing vesicles (EV) in the cytoplasm. Compared to controls, the CuCl2 treatment lowered (P < 0.05) hepatocyte enzymatic activities and increased lipid peroxidation as indicated by an increase in malondialdehyde (MDA) levels. The effects of CuCl2 were attenuated by simultaneous administration with Na2SeO3. These results indicated that the adverse effects of copper toxicity can be partially attenuated by providing a source of selenium.

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

Similar content being viewed by others

References

  1. Madsen E, Gitlin JD (2007) Copper and iron disorders of the brain. Annu Rev Neurosci 30:317–337

    Article  CAS  PubMed  Google Scholar 

  2. Gines S, Ivanova E, Seong IS, Saura CA, MacDonald ME (2003) Enhanced Akt signaling is an early pro-survival response that reflects N-methyl-D-aspartate receptor activation in Huntington’s disease knock-in striatal cells. J Biol Chem 278:50514–50522

    Article  CAS  PubMed  Google Scholar 

  3. Uriu-Adams JY, Keen CL (2005) Copper, oxidative stress, and human health. Mol Asp Med 26:268–298

    Article  CAS  Google Scholar 

  4. Fernandes A, Mira ML, Azevedo MS, Manso C (1988) Mechanisms of hemolysis induced by copper. Free Radic Res Commun 4:291–298

    Article  CAS  PubMed  Google Scholar 

  5. Sardana MK, Sassa S, Kappas A (1982) Metal ion-mediated regulation of heme oxygenase induction in cultured avian liver cells. J Biol Chem 257:4806–4811

    CAS  PubMed  Google Scholar 

  6. Ahasan HA, Chowdhury MA, Azhar MA (1994) Copper sulfate poisoning. Trop Dr 24:52–53

    CAS  Google Scholar 

  7. Britton RS, Bacon BR (1994) Role of free radicals in liver diseases and hepatic fibrosis. Hepatogastroenterology 41:343–348

    CAS  PubMed  Google Scholar 

  8. Brewer GJ (2007) A brand new mechanism for copper toxicity. J Hepatol 47:621–622

    Article  CAS  PubMed  Google Scholar 

  9. Sokol RJ, Devereaux MW, Khandwala RA, Loehr JP (1993) Abnormal hepatic mitochondrial respiration and cytochrome C oxidase activity in rats with long-term copper overload. Gastroenterology 105:178–187

    CAS  PubMed  Google Scholar 

  10. Al-Nasser IA (2000) Cadmium hepatotoxicity and alterations of the mitochondrial function. Clin Toxicol 38:407–413

    Article  CAS  Google Scholar 

  11. Rauen U, Petrat F, Sustmann R, de Groot H (2004) Iron-induced mitochondrial permeabiltiy transition in cultured hepatocytes. J Hepatol 40:607–615

    Article  CAS  PubMed  Google Scholar 

  12. Xiang LX, Shao JZ (2003) Role of intracellular Ca2+, reactive oxygen species, mitochondria transmembrane potential, and antioxidant enzymes in heavy metal-induced apoptosis in fish cells. Bull Environ Contam Toxicol 71:114–122

    Article  CAS  PubMed  Google Scholar 

  13. Pourahmad J, O’ Brien PJ (2000) A comparison of hepatocyte cytotoxic mechanisms for Cu2+ and Cd2+. Toxicology 143:263–273

    Article  CAS  PubMed  Google Scholar 

  14. Zhao M, Antunes F, Eaton JW, Brunk UT (2003) Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. Eur J Biochem 270:3778–3786

    Article  CAS  PubMed  Google Scholar 

  15. Krumschnabel G, Manzl C, Berger C, Hofer B (2005) Oxidative stress, mitochondrial permeability transition and cell death in Cu-exposed trout hepatocytes. Toxicol Appl Pharmacol 209:62–73

    Article  CAS  PubMed  Google Scholar 

  16. Rongsheng S, Wang R, Guo S, Cao H, Pan J, Li C, Shi D, Tang Z (2011) In vitro effect of copper chloride exposure on reactive oxygen species generation and respiratory chain complex activities of mitochondria isolated from broiler liver. Biol Trace Elem Res 144:668–677

    Article  Google Scholar 

  17. Garcia N, Martinez-Abundis E, Pavon N, Correa F, Chavez E (2007) Copper induces permeability transition through its interaction with the adenine nucleotide translocase. Cell Biol Int 31:893–899

    Article  CAS  PubMed  Google Scholar 

  18. Sies H (1993) Strategies of antioxidant defence. Eur J Biochem 215:213–219

    Article  CAS  PubMed  Google Scholar 

  19. Monedero-Prieto MJ, González-Pérez JM, González-Reimers E, Hernández-Pérez O, Monereo-Muñoz M, Galindo-Martín L, Quintero-Platt G, Abreu-González P (2014) Effects of selenium on liver and muscle contents and urinary excretion of zinc, copper, iron and manganese. Biol Trace Elem Res 158:224–229

    Article  CAS  PubMed  Google Scholar 

  20. Humphrey C, Pittman G (1974) A simple methylene blue-azure 2 basic fuchsin for epoxy-embedded tissue sections. Stain Technol 49:9–14

    CAS  PubMed  Google Scholar 

  21. Tang Z, Iqbal M, Cawthon D (2002) Heart and breast muscle mitochondrial dysfunction in pulmonary hypertension syndrome in broilers (Gallus domesticus). Comp Biochem Physiol A 3:527–540

    Article  Google Scholar 

  22. Bradford HF, Dodd RR (1977) Convulsions and activation of epileptic foci induced by monosodium glutamate and related compounds. Biochem Pharmacol 26:253–254

    Article  CAS  PubMed  Google Scholar 

  23. Sokol RJ, Devereaux MW, Traber MG, Shikes RH (1989) Copper toxicity and lipid peroxidation in isolated rat hepatocytes: effect of vitamin E. Pediatr Res 25:55–62

    Article  CAS  PubMed  Google Scholar 

  24. Mudassar S, Andrabi KI, Khullar M, Ganguly NK, Walia BNS (1992) Effect of exogenous copper on lipid peroxidation in rat hepatocytes. Possible involvement of protein kinase C. J Pharm Pharmacol 44:609–611

    Article  CAS  PubMed  Google Scholar 

  25. Zhang SS, Noordin MM, Rahman SO, Haron J (2000) Effects of copper overload on hepatic lipid peroxidation and antioxidant defense in rats. Vet Hum Toxicol 42:261–264

    CAS  PubMed  Google Scholar 

  26. Chen JJ, Yu BP (1994) Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radic Biol Med 17:411–418

    Article  CAS  PubMed  Google Scholar 

  27. Ferrante MC, Meli R, Mattace Raso G, Esposito E, Severino L, Di Carlo G, Lucisano A (2002) Effect of fumonisin B1 on structure and function of macrophage plasma membrane. Toxicol Lett 129:181–187

    Article  CAS  PubMed  Google Scholar 

  28. Halliwell B, Chirico S (1993) Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr 57(5Suppl):715S–724S, discussion 724S-725S

    CAS  PubMed  Google Scholar 

  29. Loumbourdis NS, Vogiatzis AK (2002) Impact of cadmium on liver pigmentary system of the frog Rana ridibunda. Ecotoxicol Environ Saf 53:52–58

    Article  CAS  PubMed  Google Scholar 

  30. Bustamante J, Bredeston L, Malanga G, Mordoh J (1993) Role of melanin as a scavenger ofactive oxygen species. Pigment Cell Res 6:348–353

    Article  CAS  PubMed  Google Scholar 

  31. Rozanowska M, Sarna T, Land EJ, Truscott TG (1999) Free radical scavenging properties of melanin interaction of eu- and pheomelanin models with reducing and oxidizing radicals. Free Radic Biol Med 26:518–525

    Article  CAS  PubMed  Google Scholar 

  32. Loumbourdis NS (2007) Liver histopathologic alterations in the frog Rana ridibunda from a small river of northern Greece. Arch Environ Contam Toxicol 53:418–425

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This project was supported by foundation of Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases (Grant No. 2013A061401013).

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhaoxin Tang.

Additional information

Rongsheng Su and Huabin Cao contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Su, R., Cao, H., Pan, J. et al. The Protective Roles of Selenium on Hepatic Tissue Ultrastructure and Mitochondrial Antioxidant Capacity in Copper-Overloaded Rats. Biol Trace Elem Res 167, 110–114 (2015). https://doi.org/10.1007/s12011-015-0293-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0293-8

Keywords

Navigation