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

The effect of ISP-I/myriocin on adenosine 3′monophosphate (3′-AMP) forming enzyme activity in carbon tetrachloride (CCl4)-induced hepatitis was examined. The 3′-AMP forming enzyme activity in mouse liver was enhanced by the treatment of CCl4. 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 CCl4. Pretreatment of mice with ISP-I/myriocin for 24 hr, significantly inhibited both the CCl4-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 CCl4, 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 CCl4-induced hepatotoxicity.