Soy isoflavones reduce acetaminophen-induced liver injury by inhibiting cytochrome P-450-mediated bioactivation and glutathione depletion and increasing urinary drug excretion in rats

Yun Ta Liu, Yu Hua Chen, Naoto Uramaru, Ai Hsuan Lin, Hui Ting Yang, Chong Kuei Lii, Hsien Tsung Yao

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Soy isoflavones (SI) are phytochemicals with various biological activities. Acetaminophen can cause acute liver injury when overdosed. In this study, to investigate the effects of SI on the metabolism and toxicity of acetaminophen in liver, rats were fed a controlled diet with or without 120 mg/kg SI-rich product for 2 weeks and were then intraperitoneally injected with acetaminophen. Cytochrome P-450 (CYP), phase II enzymes, membrane transporters, and glutathione in liver were evaluated. Acetaminophen-induced elevations in plasma alanine aminotransferase activity and decreases in liver glutathione levels were ameliorated in rats treated with SI. SI reduced hepatic CYP2E1 and CYP3A activities and acetaminophen-protein adduct contents. Hepatic UDP-glucuronosyltransferase activity and urinary acetaminophen excretion were increased by SI after acetaminophen treatment. Protein expression of multidrug-resistance-associated protein 2/3 and connexin 32 in liver, however, was not changed by SI. Our results indicate that SI-rich product may act as functional food which can reduce acetaminophen-induced hepatotoxicity.

Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalJournal of Functional Foods
Volume26
DOIs
Publication statusPublished - Oct 1 2016
Externally publishedYes

Fingerprint

drug excretion
acetaminophen
Isoflavones
Acetaminophen
isoflavones
cytochrome P-450
Cytochrome P-450 Enzyme System
Glutathione
glutathione
liver
Liver
rats
Wounds and Injuries
Pharmaceutical Preparations
connexins
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP2E1
Glucuronosyltransferase
Functional Food
Membrane Transport Proteins

Keywords

  • Acetaminophen
  • Cytochrome P450
  • Liver
  • Rats
  • Soy isoflavones

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science
  • Nutrition and Dietetics

Cite this

Soy isoflavones reduce acetaminophen-induced liver injury by inhibiting cytochrome P-450-mediated bioactivation and glutathione depletion and increasing urinary drug excretion in rats. / Liu, Yun Ta; Chen, Yu Hua; Uramaru, Naoto; Lin, Ai Hsuan; Yang, Hui Ting; Lii, Chong Kuei; Yao, Hsien Tsung.

In: Journal of Functional Foods, Vol. 26, 01.10.2016, p. 135-143.

Research output: Contribution to journalArticle

@article{0cbc2457648147519a6eb2f17103912d,
title = "Soy isoflavones reduce acetaminophen-induced liver injury by inhibiting cytochrome P-450-mediated bioactivation and glutathione depletion and increasing urinary drug excretion in rats",
abstract = "Soy isoflavones (SI) are phytochemicals with various biological activities. Acetaminophen can cause acute liver injury when overdosed. In this study, to investigate the effects of SI on the metabolism and toxicity of acetaminophen in liver, rats were fed a controlled diet with or without 120 mg/kg SI-rich product for 2 weeks and were then intraperitoneally injected with acetaminophen. Cytochrome P-450 (CYP), phase II enzymes, membrane transporters, and glutathione in liver were evaluated. Acetaminophen-induced elevations in plasma alanine aminotransferase activity and decreases in liver glutathione levels were ameliorated in rats treated with SI. SI reduced hepatic CYP2E1 and CYP3A activities and acetaminophen-protein adduct contents. Hepatic UDP-glucuronosyltransferase activity and urinary acetaminophen excretion were increased by SI after acetaminophen treatment. Protein expression of multidrug-resistance-associated protein 2/3 and connexin 32 in liver, however, was not changed by SI. Our results indicate that SI-rich product may act as functional food which can reduce acetaminophen-induced hepatotoxicity.",
keywords = "Acetaminophen, Cytochrome P450, Liver, Rats, Soy isoflavones",
author = "Liu, {Yun Ta} and Chen, {Yu Hua} and Naoto Uramaru and Lin, {Ai Hsuan} and Yang, {Hui Ting} and Lii, {Chong Kuei} and Yao, {Hsien Tsung}",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.jff.2016.07.011",
language = "English",
volume = "26",
pages = "135--143",
journal = "Journal of Functional Foods",
issn = "1756-4646",
publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - Soy isoflavones reduce acetaminophen-induced liver injury by inhibiting cytochrome P-450-mediated bioactivation and glutathione depletion and increasing urinary drug excretion in rats

AU - Liu, Yun Ta

AU - Chen, Yu Hua

AU - Uramaru, Naoto

AU - Lin, Ai Hsuan

AU - Yang, Hui Ting

AU - Lii, Chong Kuei

AU - Yao, Hsien Tsung

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Soy isoflavones (SI) are phytochemicals with various biological activities. Acetaminophen can cause acute liver injury when overdosed. In this study, to investigate the effects of SI on the metabolism and toxicity of acetaminophen in liver, rats were fed a controlled diet with or without 120 mg/kg SI-rich product for 2 weeks and were then intraperitoneally injected with acetaminophen. Cytochrome P-450 (CYP), phase II enzymes, membrane transporters, and glutathione in liver were evaluated. Acetaminophen-induced elevations in plasma alanine aminotransferase activity and decreases in liver glutathione levels were ameliorated in rats treated with SI. SI reduced hepatic CYP2E1 and CYP3A activities and acetaminophen-protein adduct contents. Hepatic UDP-glucuronosyltransferase activity and urinary acetaminophen excretion were increased by SI after acetaminophen treatment. Protein expression of multidrug-resistance-associated protein 2/3 and connexin 32 in liver, however, was not changed by SI. Our results indicate that SI-rich product may act as functional food which can reduce acetaminophen-induced hepatotoxicity.

AB - Soy isoflavones (SI) are phytochemicals with various biological activities. Acetaminophen can cause acute liver injury when overdosed. In this study, to investigate the effects of SI on the metabolism and toxicity of acetaminophen in liver, rats were fed a controlled diet with or without 120 mg/kg SI-rich product for 2 weeks and were then intraperitoneally injected with acetaminophen. Cytochrome P-450 (CYP), phase II enzymes, membrane transporters, and glutathione in liver were evaluated. Acetaminophen-induced elevations in plasma alanine aminotransferase activity and decreases in liver glutathione levels were ameliorated in rats treated with SI. SI reduced hepatic CYP2E1 and CYP3A activities and acetaminophen-protein adduct contents. Hepatic UDP-glucuronosyltransferase activity and urinary acetaminophen excretion were increased by SI after acetaminophen treatment. Protein expression of multidrug-resistance-associated protein 2/3 and connexin 32 in liver, however, was not changed by SI. Our results indicate that SI-rich product may act as functional food which can reduce acetaminophen-induced hepatotoxicity.

KW - Acetaminophen

KW - Cytochrome P450

KW - Liver

KW - Rats

KW - Soy isoflavones

UR - http://www.scopus.com/inward/record.url?scp=84979052718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979052718&partnerID=8YFLogxK

U2 - 10.1016/j.jff.2016.07.011

DO - 10.1016/j.jff.2016.07.011

M3 - Article

AN - SCOPUS:84979052718

VL - 26

SP - 135

EP - 143

JO - Journal of Functional Foods

JF - Journal of Functional Foods

SN - 1756-4646

ER -