TY - JOUR
T1 - β-Naphthoflavone-inducible cytochrome P4501A1 activity in liver microsomes of the marine safi fish (Siganus canaliculatus)
AU - Raza, Haider
AU - Otaiba, Amna
AU - Montague, William
N1 - Funding Information:
Acknowledgements-The: authors thank Professor M. M. Yousef, Prof. R. Bayoumi, Dr. Saif Al-Ghais, and the Graduate Committee of Amna Otaiba for support and encouragement during this study. The helpful suggestionso f Professor M. A. Q. Khan, Visiting Professor, Faculty of Science, UAE University, Al Ain, during the initial period of the study are acknowledged. We also wish to thank Dr. Fred F. Kadlubar, National Center for Toxicological Research, Jefferson, AR, U.S.A., for providing the facility for the HPLC analysis. Thanks are also due to K. Assainar and the Media Production Unit of the Faculty of Medicine and Health Sciences,U AE University, for assistancein the preparation of this manuscript. The study was supported, in part, by a FMHS Research CommitteeG rant.
PY - 1995/10/26
Y1 - 1995/10/26
N2 - The cytochrome P450-dependent metabolism of benzo(a)pyrene and other xenobiotics has been investigated in liver microsomes prepared from a local marine safi fish, Siganus canaliculatus. The safi fish was found to have a well-developed microsomal monooxygenase system consisting of cytochrome P450, cytochrome b5 and NADPH-cytochrome c reductase. The fish microsomal enzyme system was able to metabolize benzo(a)pyrene, 7-ethoxycoumarin and 7-ethoxyresorufin. Male fish were found to exhibit a higher monooxygenase activity than female fish. Treatment of fish with β-naphthoflavone was found to induce (2- to 4-fold) the activities of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase. HPLC analysis of the metabolites produced by incubation of benzo(a)pyrene with the liver microsomal preparation showed a predominant formation of 3-OH and 9-OH benzo(a)pyrene. There was an increased formation of benzo(a)pyrene 7,8-diol and benzo(a)pyrene 7,8,9,10-tetrol in liver microsomes prepared from β-naphthoflavone-treated fish. Western immunoblot analysis of liver microsomes from β -naphthoflavone-treated fish using an antibody to rat liver cytochrome P4501A1 (CYP1A1) suggested the presence of an inducible cytochrome P450 enzyme that was comparable with that of rat liver enzyme. Our results suggest that liver microsomes from the safi fish have multiple forms of cytochrome P450 with a specific β-naphthoflavone-inducible CYP1A1 homologous protein that can metabolize a variety of substrates.
AB - The cytochrome P450-dependent metabolism of benzo(a)pyrene and other xenobiotics has been investigated in liver microsomes prepared from a local marine safi fish, Siganus canaliculatus. The safi fish was found to have a well-developed microsomal monooxygenase system consisting of cytochrome P450, cytochrome b5 and NADPH-cytochrome c reductase. The fish microsomal enzyme system was able to metabolize benzo(a)pyrene, 7-ethoxycoumarin and 7-ethoxyresorufin. Male fish were found to exhibit a higher monooxygenase activity than female fish. Treatment of fish with β-naphthoflavone was found to induce (2- to 4-fold) the activities of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase. HPLC analysis of the metabolites produced by incubation of benzo(a)pyrene with the liver microsomal preparation showed a predominant formation of 3-OH and 9-OH benzo(a)pyrene. There was an increased formation of benzo(a)pyrene 7,8-diol and benzo(a)pyrene 7,8,9,10-tetrol in liver microsomes prepared from β-naphthoflavone-treated fish. Western immunoblot analysis of liver microsomes from β -naphthoflavone-treated fish using an antibody to rat liver cytochrome P4501A1 (CYP1A1) suggested the presence of an inducible cytochrome P450 enzyme that was comparable with that of rat liver enzyme. Our results suggest that liver microsomes from the safi fish have multiple forms of cytochrome P450 with a specific β-naphthoflavone-inducible CYP1A1 homologous protein that can metabolize a variety of substrates.
KW - HPLC
KW - benzo(a)pyrene metabolism
KW - cytochrome P450
KW - marine fish
KW - western blotting
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U2 - 10.1016/0006-2952(96)84544-8
DO - 10.1016/0006-2952(96)84544-8
M3 - Article
C2 - 7503790
AN - SCOPUS:0028972351
SN - 0006-2952
VL - 50
SP - 1401
EP - 1406
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 9
ER -