OXIDATIVE STRESS IN THE CHRONIC TOXICITY OF TCDD

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from Applicant's Abstract): Oxidative stress resulting
from increased production of reactive oxygen species have been established
as one of the mechanisms of the acute toxicity of TCDD and other halogenated
polycyclic hydrocarbons. However, no experiments have investigated the role
of oxidative stress in the chronic toxicity of these compounds. To assess
the involvement of oxidative stress in the chronic toxicity of TCDD, effects
of 26 weeks oral treatment with daily doses of 0.05 LD50 TCDD/kg and 0.005
LD50 TCDD/kg on the weight and histopathology of the liver, thymus, spleen,
pancreas and adrenal from female C57BL/6J mice will be determined following
staining with hematoxylin and eosin by two staff members in the Dept. of
Pathology, Creighton University. Measures of oxidative stress including
lipid peroxidation in the liver and extrahepatic tissue such as heart,
testes, thymus, brain adrenal glands, and kidneys (measured by the
thiobarbituric acid assay); DNA-single strand breaks in liver nuclei and
peritoneal lavage cells (measured by DNA alkaline elution technique);
production of reactive oxygen species by peritoneal lavage cells, liver
mitochondria and liver microsomes (measured by the cytochrome c and
iodonitrotetrazolium assays); production of nitric oxide (measured by
nitrite concentration assay); activity of glutathione peroxidase; and
effects on calcium and iron homeostasis will be determined following the
above treatment with TCDD. Measures of TCDD induced immunotoxicity
including secretion of interleukin-1 (IL-1) and secretion of tumor necrosis
factor-alpha (TNF-a) by peritoneal lavage cells (measured by ELISA);
secretion of interleukin-2 (IL-2) (measured by ELISA) and mixed leukocyte
response by spleen single cell suspensions (SCS); and T-lymphocyte-mediated
cytolysis (measured by 51CCr release assay) will also be determined
following treatment of female C57BL/6J mice with oral daily doses of 0.05
LD50 TCDD/kg and 0.005 LD50 TCDD/kg for 26 weeks. The data from this study
will provide a clear indication of the role of oxidative stress in the
chronic toxicity of TCDD including its most sensitive target, the immune
system.
StatusFinished
Effective start/end date4/7/973/31/00

Funding

  • National Institute of Environmental Health Sciences

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