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Effects of Perilla frutescens on modulations of CYP1A1/2, HO‐1 and activation of Nrf2 in oxidative stress‐induced hepatotoxicity (647.19)
Author(s) -
Kang Jeong Han,
Yang SungYong,
Lee KwangWon
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.647.19
Subject(s) - oxidative stress , chemistry , cyp2e1 , antioxidant , cyp1a2 , pharmacology , cytochrome p450 , oxidative phosphorylation , biochemistry , enzyme , biology
We have previously reported protective effect of Perilla leaves extract (PLE) against tert ‐butyl hydroperoxide ( t ‐BHP)‐induced liver oxidative damage in rats. t ‐BHP is known that can be metabolized to free radical intermediates by Phase I enzyme, cytochrome P450s (CYPs), and we speculate that oxidative stress was induced by t ‐BHP, which seemed to be closely linked with the oxidative metabolism mediated by CYPs. We examined the effect of the PLE about CYPs related to oxidative stress on enzyme assay such as 7‐ethoxyresorufin 0‐deethylase (EROD, CYP1A1), 7‐methoxyresorufin 0‐demethylase (MROD, CYP1A2), erythromycin N‐demethylase (ERDM, CYP3A), and p ‐nitrophenol hydroxylase (PNPH, CYP2E1) in rat liver. The pretreatment of rats with PLE (250, 500 and 1000 mg/kg b.w.) for 5 days before a single dose of t ‐BHP (i.p.; 0.5 mmol/kg). PLE was found to be a potent inhibitory effect CYP1A1/2 of oxidative stress‐induced liver. Kinetic analysis of CYP1A1/2 activities demonstrated that PLE inhibited enzyme activities by competitive or noncompetitive mechanism, respectively. Therefore, selective control of CYPs by PLE might contribute to protective effect through inhibitory CYPs activity against oxidative stress in liver. Heme oxygenase‐1 (HO‐1) is an important antioxidant phase II enzyme that plays a critical role in protection against oxidative stress. We confirmed that PLE increased induction of HO‐1 expression as well as activity in t ‐BHP‐induced liver. Also, PLE resulted in enhanced nuclear translocation and antioxidant response element (ARE)‐binding of NF‐E2‐related factor 2 (Nrf2) that induce HO‐1.