Cyclosporin a-induced lipid and protein oxidation in human B-cells and in epstein-barr virus-infected B-cells is prevented by antioxidants

Changguo Chen, Hoonbae Jeon, Thomas D. Johnston, Roberto Gedaly, Patrick P. McHugh, Dinesh Ranjan

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The incidence of post-transplant lymphoproliferative disorder (PTLD) has increased since cyclosporin A (CsA) became the mainstay of transplant immunosuppression. We have previously shown that, in addition to its potent immunosuppressive property, CsA-induced oxidative stress plays an important role in Epstein-Barr virus (EBV)-related PTLD. Using lipid hydroperoxide and malondialdehyde as markers of lipid oxidation, and protein carbonyls as markers of protein oxidation, we further investigated the in vitro effect of CsA on human B cells and EBV-infected human B cells. We found that CsA at 500 ng/ml, a relatively safe and effective blood concentration in organ transplant recipients, induced the highest lipid hydroperoxide and malondialdehyde after 10 min of treatment in time- and concentration-related kinetic studies. We also found that treatment with CsA at 500 ng/ml for 10 min increased the EBV-infected B cell protein carbonyl formation as assayed by immunoblot method. CsA-induced lipid and protein oxidation could be inhibited by vitamin E, N-acetyl cysteine, and pyrollidine dithiocarbamate. CsA significantly promoted the EBV-B cell transformation as assayed by colony counting, cell counting, and 3H-thymidine incorporation. Our recent study provides further evidence to support the hypothesis that CsA exerts direct oxidative stress in EBV-infected as well as non-EBV-infected human B cells. A greater understanding of these cellular and molecular mechanisms may benefit the clinical practice and prevention of PTLD.

Original languageEnglish
Pages (from-to)201-208
Number of pages8
JournalJournal of Investigative Surgery
Volume21
Issue number4
DOIs
StatePublished - Jul 2008

Keywords

  • Cyclosporin A
  • Epstein-Barr virus
  • Human splenocytes
  • Lipid peroxidation
  • Post-transplant lymphoproliferative disorder
  • Protein oxidation

ASJC Scopus subject areas

  • Surgery

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