Skip to main content
Log in

Possible involvement of active oxygen species in selenite toxicity in isolated rat hepatocytes

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Mechanisms of selenite cytotoxicity were examined using isolated rat hepatocytes. When selenite was added to a suspension of rat hepatocytes, intracellular reduced glutathione (GSH) was decreased and the oxygen consumption rate was increased. Subsequently, thiobarbituric acid-reactive substances (TBA-RS) and lactate dehydrogenase (LDH) leakage were increased. A ferric iron chelator, desferrioxamine (DF), and a synthetic Superoxide dismutase (SOD) mimic, desferrioxamine manganese (DFMn), reduced the selenite toxicity. These results suggest that Superoxide anion and its reactive metabolites such as the hydroxyl radical may be involved in the cytotoxicity of selenite.

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.

Similar content being viewed by others

References

  • Anundi I, Ståhl A, Högberg J (1984) Effects of selenite on O2 consumption, glutathione oxidation and NADPH levels in isolated hepatocytes and the role of redox changes in selenite toxicity. Chem Biol Interact 50: 277–288

    PubMed  Google Scholar 

  • Batist G, Katki AG, Klecker Jr RW, Myers CE (1986) Selenium-induced cytotoxicity of human leukemia cells: interaction with reduced glutathione. Cancer Res 46: 5482–5485

    PubMed  Google Scholar 

  • Bell RR, Nonavinakere VK, Soliman MRI, Early II JL (1991) Effect of in vitro treatment of rat hepatocytes with selenium, and/or cadmium on cell viability, glucose output, and cellular glutathione. Toxicology 69: 111–119

    PubMed  Google Scholar 

  • Darr D, Zarilla KA, Fridovich I (1987) A mimic of Superoxide dismutase activity based upon desferrioxamine B and manganese (IV). Arch Biochem Biophys 258: 351–355

    PubMed  Google Scholar 

  • Dougherty JJ, Hoekstra WG (1982) Stimulation of lipid peroxidation in vivo by injected selenite and lack of stimulation by selenate. Proc Soc Exp Biol Med 169: 209–215

    PubMed  Google Scholar 

  • Ganther HE (1966) Enzymic synthesis of dimethyl selenide from sodium selenite in mouse liver extract. Biochemistry 5: 1089–1098

    PubMed  Google Scholar 

  • Ganther HE (1968) Selenotrisulfides. Formation by the reaction of thiols with selenious acid. Biochemistry 7: 2898–2905

    Google Scholar 

  • Ganther HE (1971) Reduction of the selenotrisulfide derivative of glutathione to a persulfide analog by glutathione reductase. Biochemistry 10: 4089–4098

    Google Scholar 

  • Ganther HE, Corcoran C (1969) Selenotrisulfide. II. Cross-linking of reduced pancreatic ribonuclease with selenium. Biochemistry 8: 2557–2563

    PubMed  Google Scholar 

  • Garberg P, Högberg J (1987) The role of hypoxia in selenium metabolism. Biochem Pharmacol 36: 1377–1379

    PubMed  Google Scholar 

  • Garberg P, Ståhl A, Warholm M, Högberg J (1988) Studies of the role of DNA fragmentation in selenium toxicity. Biochem Pharmacol 37: 3401–3406

    PubMed  Google Scholar 

  • Högberg J, Kristoferson A (1977) A correlation between glutathione levels and cellular damage in isolated hepatocytes. Eur J Biochem 74: 77–82

    PubMed  Google Scholar 

  • Hsieh HS, Ganther HE (1975) Acid-volatile selenium formation catalyzed by glutathione reductase. Biochemistry 14: 1632–1636

    PubMed  Google Scholar 

  • Imanari T, Hirota M, Miyazaki M, Hayakawa K, Tamura Z (1977) Improved assay method for Superoxide dismutase. J Clin Exp Med (Igaku No Ayumi) 101: 496–497

    Google Scholar 

  • Imura N, Naganuma A (1978) Interaction of inorganic mercury and selenite in rabbit blood after intravenous administration. J Pharm Dyn 1: 67–73

    Google Scholar 

  • Landenstein R, Epp O, Bartels K, Jones A, Huber R, Wendel A (1979) Structure analysis and molecular model of the selenoenzyme glutathione peroxidase at 2.8 Å resolution. J Mol Biol 134: 199–218

    PubMed  Google Scholar 

  • McNeil TL, Beck LV (1968) Fluorometric estimation of GSH-OPT. Anal Biochem 22: 431–441

    PubMed  Google Scholar 

  • Naganuma A, Imura N (1980) Bis(methylmercuric) selenide as a reaction product from methylmercury and selenite in rabbit blood. Res Commun Chem Pathol Pharmacol 27: 163–173

    PubMed  Google Scholar 

  • Ohkawa H, Ohisi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by the thiobarbituric acid reaction. Anal Biochem 95: 351–358

    PubMed  Google Scholar 

  • Ray JH, Altenburg LC (1978) Sister-chromatid exchange induction by sodium selenite: dependence on the presence of red blood cells or red blood cell lysate. Mutat Res 54: 343–354

    PubMed  Google Scholar 

  • Seko Y, Saito Y, Kitahara J, Imura N (1989) Active oxygen generation by the reaction of selenite with reduced glutathione in vitro. In: Wendel A (ed) Selenium in biology and medicine. Springer, Berlin Heidelberg New York, pp 70–73

    Google Scholar 

  • Shamberger RJ (1983 a) Biological interactions of selenium with other substances. In: Shamberger RJ (ed) Biochemistry of Selenium. Plenum, New York London, pp 125–166

    Google Scholar 

  • Shamberger RJ (1983 b) Toxicity of selenium. In: Shamberger RJ (ed) Biochemistry of selenium. Plenum, New York London, pp 185–206

    Google Scholar 

  • Snyder RD (1987) Effects of sodium selenite on DNA and carcinogeninduced DNA repair in human diploid fibroblasts. Cancer Lett 34: 73–81

    PubMed  Google Scholar 

  • Thomas CE, Morehouse LA, Aust SD (1985) Ferritin and superoxide-dependent lipid peroxidation. J Biol Chem 260: 3275–3280

    PubMed  Google Scholar 

  • Whiting RF, Wei L, Stich HF (1980) Unscheduled DNA synthesis and chromosome aberrations induced by inorganic and organic selenium compounds in the presence of glutathione. Mutat Res 78: 159–169

    PubMed  Google Scholar 

  • Wróblewski F, LaDue JS (1955) Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med 90: 210–213

    PubMed  Google Scholar 

  • Young JD, Crowley C, Tucker EM (1981) Haemolysis of normal and glutathione-deficient sheep erythrocytes by selenite and tellurite. Biochem Pharmacol 30: 2527–2530

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kitahara, J., Seko, Y. & Imura, N. Possible involvement of active oxygen species in selenite toxicity in isolated rat hepatocytes. Arch Toxicol 67, 497–501 (1993). https://doi.org/10.1007/BF01969921

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01969921

Key words

Navigation