Hepatic ethoxyresorufin O-deethylase activity of liver microsomal cytochrome P-450 (CYP1A1) in young and adult rats treated with paracetamol and β-naphthoflavone

Background: Age-related differences in the ethoxyresorufin O-deethylase (EROD) activity of CYP1A1 and its inducibility in rats may determine the toxic potential of acetaminophen. This study was carried out to compare the effects of acetaminophen (APAP) and β-naphthoflavone (βNF) on CYP1A1 activity in young and adult rats.
Methods: For this purpose, young and adult rats (n = four / group) were treated with different doses of APAP. Likewise groups of young and adult rats were treated with a single dose of β-naphthoflavone (βNF, 67 mg / kg b.w). EROD was measured in microsomal fraction using resorufin as the substrate.
Results:The results showed that a single i. p. injection of APAP (25 mg / kg B.W.) failed to alter liver microsomal EROD in young and adults. Whereas, in adults treated with 250 and 450 mg APAP / kg B.W, liver CYP1A1 was elevated to about 45 and 60% respectively. The rate of CYP1A1 induction in young rats with single dose of APAP (450 mg/kg B.W) was approximately 32%. Induction in CYP1A1 was noticed 4 h after APAP injection and returned to normal levels in 24 h. The inducibility of CYP1A1 in rats treated with a toxic dose of APAP was comparable to the data obtained from animals treated βNF, 67 mg / kg b.w.
Conclusion: These results together with our previous reports indicate a similar pattern of changes in CYP1A1 in both the age-groups treated with toxic doses of APAP may suggest that the inducible CYP1A1 can equally contribute to protection against liver damage in young and adult rats.