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

more »

... nduced 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.