Abstract
We speculated that lipid peroxidation induced by tert-butyl hydroperoxide (t-BHP) in liver is closely linked with the metabolism mediated by CYPs. In this study, we have examined the effect of Perilla leaf extract (PLE) on CYPs using 7-ethoxyresorufin-O-deethylase (EROD, indicator of CYP1A1), 7-methoxyresorufin-O-demethylase (MROD, indicator of CYP1A2), erythromycin N-demethylase (ERDM, indicator of CYP3A), and p-nitrophenol hydroxylase (PNPH, indicator of CYP2E1) in rat liver. Rats orally pretreated with PLE (250, 500, and 1,000 mg/kg b.w.) for 5 days were administered with a single i.p. dose of t-BHP (0.5 mmol/kg). Kinetic analysis of CYP1A1/2 activities in t-BHP-treated liver demonstrated that PLE inhibits the enzyme activities by competitive and noncompetitive inhibitions. The pretreatment with PLE decreased the expression of CYP1A1/2 mRNA and protein compared with t-BHP treatment alone. A Phase II enzyme, heme oxygenase-1 (HO-1), is involved in hepatoprotection against oxidative damage, and we confirmed that PLE increases the levels of HO-1 mRNA and protein, as well as its activity in t-BHP-induced liver damage. PLE administration resulted in enhanced nuclear translocation and ARE binding of NF-E2-related factor 2. These findings suggest that PLE protects against t-BHP-induced hepatotoxicity through modulated activity and expression of selective CYPs, and ARE-driven induction of HO-1 expression and its activity.
| Original language | English |
|---|---|
| Pages (from-to) | 305-315 |
| Number of pages | 11 |
| Journal | Journal of the Korean Society for Applied Biological Chemistry |
| Volume | 58 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2015 Jun 1 |
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Keywords
- Cytochrome P450s
- Hepatoprotection
- HO-1
- Nrf2
- Oxidative stress
- Perilla frutescens
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Organic Chemistry
Cite this
Perilla frutescens modulates CYP1A1/2 and HO-1 and activates Nrf2 in oxidative stress-induced hepatotoxicity. / Kang, Jeong Han; Yang, Sung Yong; Ha, Jaeho; Lee, Kwang Won.
In: Journal of the Korean Society for Applied Biological Chemistry, Vol. 58, No. 3, 01.06.2015, p. 305-315.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Perilla frutescens modulates CYP1A1/2 and HO-1 and activates Nrf2 in oxidative stress-induced hepatotoxicity
AU - Kang, Jeong Han
AU - Yang, Sung Yong
AU - Ha, Jaeho
AU - Lee, Kwang Won
PY - 2015/6/1
Y1 - 2015/6/1
N2 - We speculated that lipid peroxidation induced by tert-butyl hydroperoxide (t-BHP) in liver is closely linked with the metabolism mediated by CYPs. In this study, we have examined the effect of Perilla leaf extract (PLE) on CYPs using 7-ethoxyresorufin-O-deethylase (EROD, indicator of CYP1A1), 7-methoxyresorufin-O-demethylase (MROD, indicator of CYP1A2), erythromycin N-demethylase (ERDM, indicator of CYP3A), and p-nitrophenol hydroxylase (PNPH, indicator of CYP2E1) in rat liver. Rats orally pretreated with PLE (250, 500, and 1,000 mg/kg b.w.) for 5 days were administered with a single i.p. dose of t-BHP (0.5 mmol/kg). Kinetic analysis of CYP1A1/2 activities in t-BHP-treated liver demonstrated that PLE inhibits the enzyme activities by competitive and noncompetitive inhibitions. The pretreatment with PLE decreased the expression of CYP1A1/2 mRNA and protein compared with t-BHP treatment alone. A Phase II enzyme, heme oxygenase-1 (HO-1), is involved in hepatoprotection against oxidative damage, and we confirmed that PLE increases the levels of HO-1 mRNA and protein, as well as its activity in t-BHP-induced liver damage. PLE administration resulted in enhanced nuclear translocation and ARE binding of NF-E2-related factor 2. These findings suggest that PLE protects against t-BHP-induced hepatotoxicity through modulated activity and expression of selective CYPs, and ARE-driven induction of HO-1 expression and its activity.
AB - We speculated that lipid peroxidation induced by tert-butyl hydroperoxide (t-BHP) in liver is closely linked with the metabolism mediated by CYPs. In this study, we have examined the effect of Perilla leaf extract (PLE) on CYPs using 7-ethoxyresorufin-O-deethylase (EROD, indicator of CYP1A1), 7-methoxyresorufin-O-demethylase (MROD, indicator of CYP1A2), erythromycin N-demethylase (ERDM, indicator of CYP3A), and p-nitrophenol hydroxylase (PNPH, indicator of CYP2E1) in rat liver. Rats orally pretreated with PLE (250, 500, and 1,000 mg/kg b.w.) for 5 days were administered with a single i.p. dose of t-BHP (0.5 mmol/kg). Kinetic analysis of CYP1A1/2 activities in t-BHP-treated liver demonstrated that PLE inhibits the enzyme activities by competitive and noncompetitive inhibitions. The pretreatment with PLE decreased the expression of CYP1A1/2 mRNA and protein compared with t-BHP treatment alone. A Phase II enzyme, heme oxygenase-1 (HO-1), is involved in hepatoprotection against oxidative damage, and we confirmed that PLE increases the levels of HO-1 mRNA and protein, as well as its activity in t-BHP-induced liver damage. PLE administration resulted in enhanced nuclear translocation and ARE binding of NF-E2-related factor 2. These findings suggest that PLE protects against t-BHP-induced hepatotoxicity through modulated activity and expression of selective CYPs, and ARE-driven induction of HO-1 expression and its activity.
KW - Cytochrome P450s
KW - Hepatoprotection
KW - HO-1
KW - Nrf2
KW - Oxidative stress
KW - Perilla frutescens
UR - http://www.scopus.com/inward/record.url?scp=84926323957&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926323957&partnerID=8YFLogxK
U2 - 10.1007/s13765-015-0044-8
DO - 10.1007/s13765-015-0044-8
M3 - Article
AN - SCOPUS:84926323957
VL - 58
SP - 305
EP - 315
JO - Applied Biological Chemistry
JF - Applied Biological Chemistry
SN - 2468-0834
IS - 3
ER -