| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1987: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
To elucidate the patho physiological effects of bile acids and active oxygen radicals on hepatocytes, first, the effects of bile acids on the fluidity of liver microsomal membranes were examined according to ESR-spin labelling method. Unconjugated bile acids decreased the fluidity of shallow portion of membranes which was estimated by using 5-doxyl stearic acid as a spin probe, while taurine or glycine conjugated bile acids increased the fluidity, relatively. Ethanol increased the fluidity of membranes especially at deep portion which was estimated by 12-doxyl stearic acid and ethanol enhanced the increment of the fluidity induced by conjugated bile acids, additively.
The degradation of spin probes as free radicals in plasma membranes of isolated hepatocytes was also investigated by using ESR. The regradation rate was influenced by both hepato-cellular antioxidants content and temperature. The correlation between the rate and the fluidity was also demonstrated.
On the other hand, the parado xical effects of oxygen and calcium on hepatocytes which were well-known as oxygen(calcium) paradoxes were examined to elucidate the involvement of oxygen radicals, mainly superoxides(O_2 ^-),in hepatocellular damages. Because O_2 ^- formation was enhanced by hyperbaric condition, the presence of Ca ^<++> and membrane damages, drugs such as dismutase of active oxygen, calcium antagonist and membrane stabillizer were effective in protecting against cell injury in these paradoxes. Although ESR spin trapping of oxygen radicals was performed, radical addacts were not available in isolated hepatocytes.
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