Abstract

HYPOTHESIS: The hepatotoxic effects of hyperthermia (41-43 degrees) are primarily the result of lipid peroxidation of cellular phospholipids. Moreover, a major source of oxygen radical is through the normal catalytic action of xanthine oxidase. Also, effects on the liver will vary with several factors: a) temperature and time at temperature, b) hepatic glutathione content and c) normal liver vs. liver with cancer. The following specific objectives are designed to test this hypothesis: 1. The perfused rat liver will be used to study the effects of hyperthermia, 41-43 degrees, on the efflux of glutathione disulfide (GSSG), malonaldehyde (MDA), hydroperoxide and lysomsomal enzymes from the normal liver and liver with cancer. 2. Study the effects of temperature 35-45 degrees on the invitro activity of the enzymes xanthine oxidase with respect to generation of superoxide, superoxide dismutase (SOD) and lgutathione peroxidase. 3. Use the perfused rat liver, normal and with cancer, to study whether the effects of heat on the liver observed in Aim 1 can be favorably changed by use of allopurinol, addition of palmitate or octanoate, or addition of N-acetylcysteine or methionine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041316-03
Application #
3181692
Study Section
Radiation Study Section (RAD)
Project Start
1985-12-01
Project End
1988-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226

  Publications

Powers, R H; Stadnicka, A; Kalbfleish, J H et al. (1992) Involvement of xanthine oxidase in oxidative stress and iron release during hyperthermic rat liver perfusion. Cancer Res 52:1699-703
Skibba, J L; Powers, R H; Stadnicka, A et al. (1991) Oxidative stress as a precursor to the irreversible hepatocellular injury caused by hyperthermia. Int J Hyperthermia 7:749-61
Skibba, J L; Powers, R H; Stadnicka, A et al. (1990) Lipid peroxidation caused by hyperthermic perfusion of rat liver. Biochem Pharmacol 40:1411-4
Skibba, J L; Stadnicka, A; Kalbfleisch, J H et al. (1989) Effects of hyperthermia on xanthine oxidase activity and glutathione levels in the perfused rat liver. J Biochem Toxicol 4:119-25
Skibba, J L; Stadnicka, A; Kalbfleisch, J H (1989) Hyperthermic liver toxicity: a role for oxidative stress. J Surg Oncol 42:103-12
Skibba, J L; Sonsalla, J C; Kalbfleisch, J H (1987) Hyperthermic liver perfusion and release of lysosomal enzymes. J Surg Res 43:558-64