13-cis-Retinoic Acid Affects Oxidation and DNA Damage in Oxidative-Positive SLE Lymphocytes But May Not Be Useful for Therapy

P. J. Benke, P. Belmar, E. Tozman, G. Monroe, C. Mauldin, J. Drisko

Research output: Contribution to journalArticle

Abstract

13-cis-Retinoic acid (13-CRA), a water-soluble vitamin A analog and 5'-lipoxygenase inhibitor, was tested in vitro for effects on excess oxidative metabolism and DNA damage in mitogen-stimulated lymphocytes from patients with systemic lupus erythematosus (SLE), because other 5'-lipoxygenase enzyme inhibitors were shown to lower the excess oxidative metabolism in SLE cells. Excess chemiluminescence (CL) was abolished within minutes after the addition of 1 x 10-6 M 13-CRA in five of five CL-positive mitogen-stimulated SLE lymphocytes, and was lowered in five of eight samples after 48 to 72 h culture. Similarly, low concentrations of 13-CRA for 48-72 h largely prevented the S1 nuclease-sensitive DNA changes/DNA damage observed in CL-positive lupus lymphocytes in vitro. However, 13-CRA did not affect DNA damage in four of four CL-negative lymphocyte samples. 13-CRA, like other retinoic acid compounds, was known to stimulate B-cell activities in vivo and in vitro but effects on dividing lupus T cells had not been studied. 13-CRA further inhibited the diminished PHA-stimulated lupus T-cell growth in tissue culture at a concentration of 9 x 10-6 M in three of five lupus lymphocyte samples. 13-CRA has positive and negative effects on multiple aspects of the immune system and it is not clear whether 13-CRA will have positive or adverse clinical effects on SLE patients. Close attention to vitamin A and vitamin 'supplements' in patients with SLE may answer this question.

Original languageEnglish (US)
Pages (from-to)13-24
Number of pages12
JournalBiochemical Medicine and Metabolic Biology
Volume49
Issue number1
DOIs
StatePublished - Feb 1 1993

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry

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