Hepatic ethoxyresorufin O-deethylase activity of liver microsomal cytochrome P-۴۵۰ (CYP۱A۱) in young and adult rats treated with paracetamol and β-naphthoflavone

Background: Age-related differences in the ethoxyresorufin O-deethylase (EROD) activity of CYP۱A۱ 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 CYP۱A۱ 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, ۶۷ 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 (۲۵ mg / kg B.W.) failed to alter liver microsomal EROD in young and adults. Whereas, in adults treated with ۲۵۰ and ۴۵۰ mg APAP / kg B.W, liver CYP۱A۱ was elevated to about ۴۵ and ۶۰% respectively. The rate of CYP۱A۱ induction in young rats with single dose of APAP (۴۵۰ mg/kg B.W) was approximately ۳۲%. Induction in CYP۱A۱ was noticed ۴ h after APAP injection and returned to normal levels in ۲۴ h. The inducibility of CYP۱A۱ in rats treated with a toxic dose of APAP was comparable to the data obtained from animals treated βNF, ۶۷ mg / kg b.w. Conclusion: These results together with our previous reports indicate a similar pattern of changes in CYP۱A۱ in both the age-groups treated with toxic doses of APAP may suggest that the inducible CYP۱A۱ can equally contribute to protection against liver damage in young and adult rats.

Keywords:

Age , CYP۱A۱ , Paracetamol , EROD , Hepatotoxicity