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 activity and cytochrome P-450 level in the livers of rats of various ages. We tried to investigate the phases of heme oxygenase activity, both spontaneous and caused by typical MFO inducers in the lifetime of the rat. Wistar male rats aged 0.5, 1, 2, 4, 8, 12, 20 and 28 months received phenobarbital (50 mg/kg) twice, 3 and 2 days before being killed. beta-Naphthoflavone and dexamethasone were given three times: 3, 2 and 1 day before decapitation 20 mg/kg and 10 mg/kg, respectively). The highest heme oxygenase activity is observed in intact 2-week-old animals (1.16+/-0.038 nM/h per mg protein). Before maturity this activity decreases slightly up to the 2nd month of life. Then it stabilizes and remains virtually unchanged till the 8th month of life (1.02+/-0.03). Afterwards 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 animals. We have found that some typical MFO inducers can modify HO activity. While phenobarbital stimulates HO activity only in premature animals (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 activity in all the groups studied. Dexamethasone, as a physiological inducer of the MFO system, modifies HO activity very characteristically. It induces this activity until the 2nd month of life and then its inducibility appears to remain unchanged. Correlations between HO activity, ALAS activity and cytochrome P-450 levels still need to be investigated to elucidate these problems.