Age-related changes in distribution of cytochrome P-450 in the hepatic lobule of the rat.

The effect of age on distribution of the phenobarbital-inducible forms of cytochrome P-450 IIBI and IIB2 in the hepatic lobule was investigated immunohistochemically by the avidin-biotin-peroxidase complex (ABC) method in male rats of various ages pretreated with phenobarbital. Exposure of liver sections to anti-cytochrome P-450 serum resulted in intense immunostaining in centrilobular hepatocytes but produced staining of weaker intensity in periportal cells in phenobarbital-treated rats, while in livers of nontreated animals, no significant immunoreactivity was detectable. Difference in the intensity of immunostaining between the centrilobular cells and the periportal ones was statistically significant in the liver of 3 and 13 month rats. By contrast, in the 30 month rat liver, intensity of immunostaining was greatly reduced in both the centrilobular and the periportal cells; no significant difference was detected in the intensity of staining between these cells. Throughout the three age-groups, a significant decrease with age was evident in the content of the immunoreactive cytochrome P-450 isozymes IIB1 and IIB2 in both the centrilobular cells and the periportal ones. The results show that the administration of phenobarbital causes an increase in the content of these cytochrome P-450 isozymes in greater amount in the centrilobular hepatocytes than in the periportal cells in the liver lobule and that the content of cytochrome P-450 isozymes induced by the phenobarbital administration decreases with age in male rats.