The effects of anti-TNF-alpha antibody and dexamethasone on TCDD-induced oxidative stress in mice

N. Z. Alsharif, E. Hassoun, M. Bagchi, T. Lawson, S. J. Stohs

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Abstract

Recent studies have implicated tumor necrosis factor α(TNF-α) in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Since TNF-α sensitizes and activates phagocytic cells to agents that induce them to release reactive oxygen species, TNF-α may act as an amplifying loop in TCDD-induced oxidative stress (OS). Therefore, the effects of anti-TNF-α antibody (40 μg/mouse) and dexamethasone (2 mg/kg) treatment on TCDD-induced OS as measured by DNA single-strand breaks (SSB) in hepatic nuclei, lipid peroxidation in hepatic mitochondria and microsomes, and activation of peritoneal lavage cells (PLC) in C57BL/6J mice were studied. One day after treatment with 125 μg TCDD/kg, anti-TNF-α resulted in 70, 27, 33 and 21% decreases in DNA-SSB, mitochondrial and microsomal lipid peroxidation and PLC activation, respectively, relative to TCDD-treated mice. Dexamethasone produced 8, 32, 35 and 9% decreases in DNA-SSB, mitochondrial and microsomal lipid peroxidation and PLC activation, respectively, in TCDD-treated animals. The combination of anti-TNF-α and dexamethasone resulted in 67, 55, 61 and 25% decreases in the above parameters of OS, respectively. The results suggest that TNF-α release may play a role in sensitizing and activating phagocytic cells following treatment with TCDD, contributing to the overall OS of animals following exposure to TCDD.

Original languageEnglish (US)
Pages (from-to)127-136
Number of pages10
JournalPharmacology
Volume48
Issue number2
DOIs
Publication statusPublished - Jan 1 1994

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Keywords

  • 2,3,7,8-tetrachlorodibenzo-p-dioxin
  • Anti-TNF-α antibody
  • DNA damage
  • Dexamethasone
  • Lipid peroxidation
  • Oxidative stress
  • Reactive oxygen species
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Pharmacology

Cite this

Alsharif, N. Z., Hassoun, E., Bagchi, M., Lawson, T., & Stohs, S. J. (1994). The effects of anti-TNF-alpha antibody and dexamethasone on TCDD-induced oxidative stress in mice. Pharmacology, 48(2), 127-136. https://doi.org/10.1159/000139171