Role of cytochrome P-450 in schisandrin B-induced antioxidant and heat shock responses in mouse liver.
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.
Chiu
Po Yee
PY
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Mak
Duncan H F
DH
Poon
Michel K T
MK
Ko
Kam Ming
KM
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
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