TY - JOUR
T1 - Induction of propranolol metabolism by the azo dye sudan III in rats
AU - Ishida, Ryozo
AU - Obara, Sakae
AU - Masubuchi, Yasuhiro
AU - Narimatsu, Shizuo
AU - Fujita, Shoichi
AU - Suzuki, Tokuji
N1 - Funding Information:
Acknowledgements-We are gratefult o Miss C. Tsuruoka and Miss R. Gohda for their valuablet echnicala ssistance. The study was supportedi n part by Grant in Aid for ScientificR esearchf rom the Ministry of Education,S cience and Culture of Japan.
PY - 1992/6/9
Y1 - 1992/6/9
N2 - Effects of the azo dye sudan III, an inducer of cytochrome P450 isozymes belonging to the CYP1A subfamily, on propranolol (PL) in vitro and in vivo metabolism were investigated in rats. The kinetic parameters of the activity for each metabolic pathway were determined in liver microsomes from control and sudan III-treated rats. Sudan III pretreatment increased extensively PL 4-hydroxylase, 5-hydroxylase and N-desisopropylase activities at high but not at low PL concentrations. On the other hand, kinetic parameters of 7-hydroxylase activity were not affected by sudan III pretreatment. Sudan III pretreatment decreased blood concentrations of PL after intraportal infusion of PL at high doses (12.5 and 20 mg/kg), but not at a low dose (5 mg/kg). These observations were consistent with data obtained from the in intro studies showing that sudan III pretreatment induced low-affinity but not high-affinity cytochrome P450 isozymes involved in PL metabolism in rat liver microsomes.
AB - Effects of the azo dye sudan III, an inducer of cytochrome P450 isozymes belonging to the CYP1A subfamily, on propranolol (PL) in vitro and in vivo metabolism were investigated in rats. The kinetic parameters of the activity for each metabolic pathway were determined in liver microsomes from control and sudan III-treated rats. Sudan III pretreatment increased extensively PL 4-hydroxylase, 5-hydroxylase and N-desisopropylase activities at high but not at low PL concentrations. On the other hand, kinetic parameters of 7-hydroxylase activity were not affected by sudan III pretreatment. Sudan III pretreatment decreased blood concentrations of PL after intraportal infusion of PL at high doses (12.5 and 20 mg/kg), but not at a low dose (5 mg/kg). These observations were consistent with data obtained from the in intro studies showing that sudan III pretreatment induced low-affinity but not high-affinity cytochrome P450 isozymes involved in PL metabolism in rat liver microsomes.
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U2 - 10.1016/0006-2952(92)90332-D
DO - 10.1016/0006-2952(92)90332-D
M3 - Article
C2 - 1376995
AN - SCOPUS:0026769890
SN - 0006-2952
VL - 43
SP - 2489
EP - 2492
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 11
ER -