title: Role of cytochrome P-450 in schisandrin B-induced antioxidant and heat shock responses in mouse liver.
abstract: In order to explore the role of cytochrome P-450 (P-450) in schisandrin B (Sch B)-induced antioxidant and heat shock responses, the effect of 1-aminobenzotriazole (ABT, a broad spectrum inhibitor of P-450) on hepatic mitochondrial glutathione antioxidant status (mtGAS) and heat shock protein (Hsp)25/70 expression was examined in Sch B-treated mice. The non-specific and partial inhibition of cytochrome P-450 (P-450) by ABT pretreatment significantly caused a protraction in the time-course of Sch B-induced enhancement in hepatic mitGAS and Hsp25/70 expression in mice. Using mouse liver microsomes as a source of P-450, Sch B, but not dimethyl diphenyl bicarboxylate (a non-hepatoprotective analog of Sch B), was found to serve as a co-substrate for the P-450-catalyzed NADPH oxidation reaction, with a concomitant production of oxidant species. Taken together, the results suggest that oxidant species generated from P-450-catalyzed reaction with Sch B may trigger the antioxidant and heat shock responses in mouse liver.
authors.affiliation: Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Po Yee
authors.initials: PY
authors.lastname: Chiu
authors.forename: Duncan H F
authors.initials: DH
authors.lastname: Mak
authors.forename: Michel K T
authors.initials: MK
authors.lastname: Poon
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants; D034242:Cyclooctanes / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018869:Heat-Shock Response / Q000187:drug effects*; D017705:Lignans / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D029633:Schisandraceae / Q000737:chemistry; D014230:Triazoles / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D034242:Cyclooctanes; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D017705:Lignans; D011083:Polycyclic Compounds; D014230:Triazoles; C015499:schizandrin B; C033020:1-aminobenzotriazole; D009249:NADP; D003577:Cytochrome P-450 Enzyme System