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

Naser 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
Pages (from-to)127-136
Number of pages10
JournalPharmacology
Volume48
Issue number2
StatePublished - 1994

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Dexamethasone
Oxidative Stress
Tumor Necrosis Factor-alpha
Antibodies
Peritoneal Lavage
Single-Stranded DNA Breaks
Lipid Peroxidation
Phagocytes
Polychlorinated Dibenzodioxins
Liver
Microsomes
Inbred C57BL Mouse
Reactive Oxygen Species
Mitochondria
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology

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The effects of anti-TNF-alpha antibody and dexamethasone on TCDD-induced oxidative stress in mice. / Alsharif, Naser Z.; Hassoun, E.; Bagchi, M.; Lawson, T.; Stohs, S. J.

In: Pharmacology, Vol. 48, No. 2, 1994, p. 127-136.

Research output: Contribution to journalArticle

Alsharif, NZ, Hassoun, E, Bagchi, M, Lawson, T & Stohs, SJ 1994, 'The effects of anti-TNF-alpha antibody and dexamethasone on TCDD-induced oxidative stress in mice', Pharmacology, vol. 48, no. 2, pp. 127-136.
Alsharif, Naser Z. ; Hassoun, E. ; Bagchi, M. ; Lawson, T. ; Stohs, S. J. / The effects of anti-TNF-alpha antibody and dexamethasone on TCDD-induced oxidative stress in mice. In: Pharmacology. 1994 ; Vol. 48, No. 2. pp. 127-136.
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