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Pharmacology. 1994 Feb;48(2):127-36.

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

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  • 1Department of Pharmaceutical Sciences, Creighton University Health Sciences Center, Omaha, Nebr.

Abstract

Recent studies have implicated tumor necrosis factor alpha (TNF-alpha) in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Since TNF-alpha sensitizes and activates phagocytic cells to agents that induce them to release reactive oxygen species, TNF-alpha may act as an amplifying loop in TCDD-induced oxidative stress (OS). Therefore, the effects of anti-TNF-alpha antibody (40 micrograms/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 micrograms TCDD/kg, anti-TNF-alpha 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-alpha and dexamethasone resulted in 67, 55, 61 and 25% decreases in the above parameters of OS, respectively. The results suggest that TNF-alpha 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.

PMID:
8134404
[PubMed - indexed for MEDLINE]
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