The objectives of the proposed research are to investigate the effects of ozone exposure under altered nutritional status - in this case dietary Vitamin E deficiency, Selenium deficiency and a combination of each, on: (1) pulmonary antioxidant defense mechanisms (2) lipid peroxidation potential (3) the levels of prostalandins, prostacyclins, thromboxanes and leukotriens (4) the activities of enzymes involved in the metabolism of arachiodonic acid and (5) cooxidarion of precarcinogens by prostaglandin synthetase reaction of rat lung. The hypothesis to be tested is that uncontrolled lipid peroxitation, a potential consequences of oxidant stress under inadequate vitamin E and selenium, nutrition can lead to damage to the pulmonary cells, subcellular organells and lung metaboolic funtions including prostaglandin metabolism. In view of the potential detrimental effects of ozone toxicity under antioxidant deficiency, both in vivo and in vitro procedures will be utilized to evaluate aspects of lung's susceptibility to membrane lipid peroxidase, its response to mutagenic and/or carcinogenic insult resulting from oxidative metabolism of polycyclic aromatic hydrocarbons and the effects of prostaglandin like endoperoxides formed during peroxodation of polyunsaturated fatty acids. The research methods to be employed include, thinlayer, high pressure liquid, and gas, chromatographic techniques for the analysis of arachidonic acid metabolites. Other procedures include polargrahic, spectrophotometric, and liquid scintillation spectrometric methods. Information obtained in these studies should enable us to understand not only the exact mechanism(s) by which Vitamin E and Selenium modulate arachiodonic acid metabolism but also their protective effects against oxidant stress. The long term objectives are to study the effects of oxidant stress under inadequate Vitamin E and Selenium nutrition on leukotriene biosynthesis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
5K04HL001240-05
Application #
3073708
Study Section
Toxicology Study Section (TOX)
Project Start
1983-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Organized Research Units
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
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