Skip to main content
SpringerLink
Log in

Prevention of oxidation and apoptosis in human peripheral blood mononuclear cells exposed to calcium dobesilate

  • Original Articles
  • Published:
International Journal of Angiology

Abstract

The antioxidant effects of calcium dobesilate (CD) (Doxium®) were investigated in relation to the oxidative status, apoptosis, andin vitro proliferation of human peripheral blood mononuclear cells (PBMC) isolated from healthy donors. Calcium dobesilate alone did not modify cell growthin vitro until it reached 10 µM. This molecule counteracted oxidative damage generated by the highly reducing sugar 2-deoxy-D-ribose (dR) and was shown to reduce apoptosis by delaying both membrane permeability changes and DNA fragmentation. Calcium dobesilate (10 µM) was effective in a time-dependent manner on several parameters, representative of the cellular oxidative status. In particular, CD significantly increased the activity of glutathione S-transferase (GST) after 3 days of treatment and also the activity of γ-glutamyltransferase (γ-GT). Both of these enzymes are known to be involved in the glutathione (GSH) metabolic cycle. This enzymatic behavior was reversed after 7 days of treatment, with a significant GST decrease and a γ-GT activation. After 7 days of CD exposure, the intracellular GSH content was enhanced and this resulted in a dramatic decrease of lipid peroxidation, underlining the powerful antioxidant properties of CD in human PBMC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anderson D, Yu TW, Phillips BJ, Schmezer P (1994) The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay. Mutat Res 307:261–271.

    PubMed  Google Scholar 

  2. Barbieri D, Grassilli E, Monti D, et al. (1994) D-ribose and deoxy-D-ribose induce apoptosis in human quiescent peripheral blood mononuclear cells. Biochem Biophys Res Commun 201:1109–1116.

    PubMed  Google Scholar 

  3. Brunet J, Farine JC, Garay RP, Haennert P (1998) In vitro oxidant properties of calcium dobesilate. Fundam Clin Pharmacol 12:205–212.

    PubMed  Google Scholar 

  4. Brunet J, Farine JC, Garay RP, Hannaert P (1998) Angioprotective action of calcium dobesilate against the increased capillary permeability induced by reactive oxigen species in the rat pertitoneal cavity. Eur J Pharmacology 358:213–220.

    Google Scholar 

  5. Curcio F, Ceriello A (1992) Decreased cultured endothelial cell proliferation in high glucose medium is reversed by antioxidants: New insights on the pathophysiological mechanisms of diabetic vascular complications. In Vitro Cell Dev Biol Anim 28A:787–790.

    Google Scholar 

  6. Graber R, Losa GA (1989) Subcellular localization and kinetic properties of phosphatidylinositol 4,5 bisphosphate phospholipase C and inositol phosphates enzymes from human peripheral blood mononuclear cells. Enzyme 14:17–26.

    Google Scholar 

  7. Graber R, Losa GA (1995a) Changes in the activities of signal transduction and transport membrane enzymes in CEM lymphoblastoid cells by glucocorticoid-induced apoptosis. Anal Cell Pathol 8:159–176.

    PubMed  Google Scholar 

  8. Harris ED (1992) Regulation of antioxidant enzymes. FASEB J 6:2675–2683.

    PubMed  Google Scholar 

  9. Lieberman MW, Barrios R, Carter BZ, et al. (1995) Gamma-glutamyl transpeptidase. What does the organization and expression of a multipromoter gene tell us about its functions? Am J Pathol 147:1175–1185.

    PubMed  Google Scholar 

  10. Lorenzi M, Montisano DF, Toledo S, Wong HC (1987a) Increased single strand breaks in DNA of lymphocytes from diabetic subjects. J Clin Invest 79:656–656.

    Google Scholar 

  11. Lorenzi M, Nordberg JA, Toledo S (1987b) High glucose prolongs cell-cycle traversal of cultured human endothelial cells. Diabetes 36:1261–1267.

    PubMed  Google Scholar 

  12. Losa GA, Morell A, Barandun S (1982) Correlations between enzymatic and immunologic properties of human peripheral blood mononuclear cells. Am J Pathol 107:191–201.

    PubMed  Google Scholar 

  13. McCaughan FM, Brown AL, Harrison DJ (1994) The effect of glutathione-S-transferase P on the growth of the Jurkat human T cell line. J Pathol 172:357–362.

    PubMed  Google Scholar 

  14. Morgenstern R, Meijer J, DePierre JW, Ernster J (1980) Characterization of rat-liver microsomal glutathione-S-transferase activity. Eur J Biochem 104:167–174.

    PubMed  Google Scholar 

  15. Morrow CS, Cowan KH (1990) Glutathione-S-transferases and drug resistance. Cancer Cells 2:15–22.

    PubMed  Google Scholar 

  16. Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocytes apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 139:271–279.

    PubMed  Google Scholar 

  17. Poli G, Gravela E, Albano E, Dianziani MU (1979) Studies on fatty liver with isolated hepatocytes: II. The action of carbon tetrachloride on lipid peroxidation, protein and triglycerides synthesis and secretion. Exp Molec Pathol 30:113–127.

    Google Scholar 

  18. Tew KD (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res 54:4313–4320.

    PubMed  Google Scholar 

  19. Zunica G, Marini M, Brunelli MA, Chiricolo M, Franceschi C (1986) D-ribose inhibits DNA repair synthesis in human lymphocytes. Biochem Biophys Res Commun 138:673–678.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratorio di Patologia Cellulare, Instituto Cantonale di Patologia, 6601, CH-Locarno, Switzerland

    Gabriele A. Losa PhD & Riccardo Graber

  2. OM Pharma, CH-1217, Meyrin, Switzerland

    Jean-Claude Farine

Authors
  1. Gabriele A. Losa PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Riccardo Graber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean-Claude Farine
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Losa, G.A., Graber, R. & Farine, JC. Prevention of oxidation and apoptosis in human peripheral blood mononuclear cells exposed to calcium dobesilate. International Journal of Angiology 8 (Suppl 1), S11–S15 (1999). https://doi.org/10.1007/BF01619843

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01619843

Keywords

Search

Navigation