EFFECTS OF AGE, PHENOBARBITAL, BETA-NAPHTHOFLAVONE AND DEXAMETHASONE ON RAT HEPATIC HEME OXYGENASE

There is a wide range of change in both microsomal heme oxygenase acti vity and cytochrome P-450 level in the livers of rats of various ages. We tried to investigate the phases of heme oxygenase activity, both s pontaneous and caused by typical MFO inducers in the lifetime of the r at. Wistar male rats aged 0.5, 1, 2, 4, 8, 12, 20 and 28 months receiv ed phenobarbital (50 mg/kg) twice, 3 and 2 days before being killed. b eta-Naphthoflavone and dexamethasone were given three times: 3, 2 and 1 day before decapitation 20 mg/kg and 10 mg/kg, respectively). The hi ghest heme oxygenase activity is observed in intact 2-week-old animals (1.16+/-0.038 nM/h per mg protein). Before maturity this activity dec reases slightly up to the 2nd month of life. Then it stabilizes and re mains virtually unchanged till the 8th month of life (1.02+/-0.03). Af terwards HO activity tends to increase until the 28th month of life (1 .10+/-0.06), but does not reach the level observed in the 2-week-old a nimals. We have found that some typical MFO inducers can modify HO act ivity. While phenobarbital stimulates HO activity only in premature an imals (1.42+/-0.056; 1.30+/-0.059 and 1.13+/-0.035, respectively in 0. 5-, 1- and 2-month-old animals), beta-naphthoflavone enhances HO activ ity in all the groups studied. Dexamethasone, as a physiological induc er of the MFO system, modifies HO activity very characteristically. It induces this activity until the 2nd month of life and then its induci bility appears to remain unchanged. Correlations between HO activity, ALAS activity and cytochrome P-450 levels still need to be investigate d to elucidate these problems.