Anti-malondialdehyde antibodies in MRL+/+ mice treated with trichloroethene and dichloroacetyl chloride: Possible role of lipid peroxidation in autoimmunity

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Abstract

Trichloroethene (TCE) and one of its metabolites dichloroacetyl chloride (DCAC) are known to induce/accelerate autoimmune (AI) response in MRL+/+ mice as evident from anti-nuclear, anti-ssDNA, anti-cardiolipin, and DCAC-specific antibodies in the serum (Khan et al., Toxicol. Appl. Pharmacol. 134, 155-160, 1995). In the present study, we measured anti-malondialdehyde antibodies (AMDA) in the serum of TCE- or DCAC-treated mice in order to understand the contribution of lipid peroxidation to this AI response. Female MRL+/+ mice (5 weeks old) received ip injections of 10 mmol/kg TCE or 0.2 mmol/kg of DCAC in corn oil (100 μl) every 4th day for 6 weeks, while controls received an equal volume of vehicle only, and AMDA was measured in the sera of these animals by an ELISA established in our laboratory. While TCE treatment caused only marginal induction of AMDA, DCAC treatment elicited a significant AMDA response. Furthermore, a time-response study of DCAC (0.2 mmol/kg, every 4th day, for 2, 4, 6, or 8 weeks) showed an induction of AMDA (3/4) after 4 weeks of treatment, which was even greater at both 6 and 8 weeks of DCAC treatment (5/5). These findings were further substantiated by the presence of AMDA in systemic lupus erythematosus-prone MRL-1pr/1pr mice as early as 6 weeks of age. Presence of AMDA, as observed in this study, not only indicates increased lipid peroxidation (oxidative stress), but also suggests a putative role of oxidative stress in inflammatory autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)88-92
Number of pages5
JournalToxicology and Applied Pharmacology
Volume170
Issue number2
DOIs
StatePublished - Jan 15 2001

Keywords

  • Anti-malondialdehyde antibodies
  • Autoimmunity
  • Dichloroacetyl chloride
  • Lipid peroxidation
  • Trichloroethene

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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