Modification of 3'-AMP Forming Enzyme Activity by a Potent lmmunosuppressant, ISP-I/Myriocin, in Liver of Mice Treated with Carbon Tetrachloride

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The effect of ISP-I/myriocin on adenosine 3'-monophosphate(3'-AMP)forming enzyme activity in carbon tetrachloride(CCl_4)-induced hepatitis was examined. The 3'-AMP forming enzyme activity in mouse liver was enhanced by the treatment of CCl_4. The increase in the activity in cytosol may result from the leakage of the enzyme from mitochondria via the damage of mitochondrial membrane induced by CCl_4. Pretreatment of mice with ISP-I/myriocin for 24 hr, significantly inhibited both the CCl_4-induced activities of serum alanine aminotransferase and the 3'-AMP forming enzyme in the supernatant of liver homogenate prepared immediately after the organ excision. These results suggest that the inhibitory effects of ISP-I/myriocin may be due to inhibition of lipid peroxidation of intracellular membranes caused by CCl_4, in turn inhibiting the leakage of the 3'-AMP forming enzyme from mitochondria to cytosol. Our results demonstrated for the first time that ISP-I/myriocin has a protective effect on the CCl_4-induced hepatotoxicity.
公益社団法人日本薬学会の論文
2001-06-01