Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury

Young Woo Kim, Sung Min Lee, Sang Mi Shin, Se Jin Hwang, Janie S. Brooks, Hee Eun Kang, Myung Gull Lee, Sang Chan Kim, Sang Geon Kim

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Iron-overload disorders cause hepatocyte injury and inflammation by oxidative stress, possibly leading to liver fibrosis and hepatocellular carcinoma. This study investigated the efficacy of sauchinone, a bioactive lignan, in preventing iron-induced liver injury and explored the mechanism of sauchinone's activity. To create iron overload, mice were injected with phenylhydrazine, and the effects on hepatic iron and histopathology were assessed. Phenylhydrazine treatment promoted liver iron accumulation and ferritin expression, causing hepatocyte death and increased plasma arachidonic acid (AA). Sauchinone attenuated liver injury (EC50 = 10 mg/kg) and activated AMPK in mice. Treatment of hepatocytes with iron and AA simulated iron overload conditions: iron + AA synergistically amplified cytotoxicity, increasing H2O2 and the mitochondrial permeability transition. Sauchinone protected hepatocytes from iron + AA-induced cytotoxicity, preventing the induction of mitochondrial dysfunction and apoptosis (EC50 = 1 μM), similar to the result using metformin. Sauchinone treatment activated LKB1, which led to AMPK activation: these events contributed to cell survival. Evidence of cytoprotection by LKB1 and AMPK activation was revealed in the reversal of sauchinone's restoration of the mitochondrial membrane potential by either dominant negative mutant AMPKα or chemical inhibitor. In conclusion, sauchinone protects the liver from toxicity induced by iron accumulation, and sauchinone's effects may be mediated by LKB1-dependent AMPK activation.

Original languageEnglish
Pages (from-to)1082-1092
Number of pages11
JournalFree Radical Biology and Medicine
Volume47
Issue number7
DOIs
Publication statusPublished - 2009 Oct 1

Fingerprint

Lignans
AMP-Activated Protein Kinases
Oxidative stress
Liver
Oxidative Stress
Iron
Wounds and Injuries
Arachidonic Acid
Iron Overload
Hepatocytes
Chemical activation
Cytotoxicity
Cytoprotection
sauchinone
Mitochondrial Membrane Potential
Metformin
Ferritins
Liver Cirrhosis
Hepatocellular Carcinoma
Permeability

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Kim, Young Woo ; Lee, Sung Min ; Shin, Sang Mi ; Hwang, Se Jin ; Brooks, Janie S. ; Kang, Hee Eun ; Lee, Myung Gull ; Kim, Sang Chan ; Kim, Sang Geon. / Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury. In: Free Radical Biology and Medicine. 2009 ; Vol. 47, No. 7. pp. 1082-1092.
@article{57642e02ad834d898ac18223d9942228,
title = "Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury",
abstract = "Iron-overload disorders cause hepatocyte injury and inflammation by oxidative stress, possibly leading to liver fibrosis and hepatocellular carcinoma. This study investigated the efficacy of sauchinone, a bioactive lignan, in preventing iron-induced liver injury and explored the mechanism of sauchinone's activity. To create iron overload, mice were injected with phenylhydrazine, and the effects on hepatic iron and histopathology were assessed. Phenylhydrazine treatment promoted liver iron accumulation and ferritin expression, causing hepatocyte death and increased plasma arachidonic acid (AA). Sauchinone attenuated liver injury (EC50 = 10 mg/kg) and activated AMPK in mice. Treatment of hepatocytes with iron and AA simulated iron overload conditions: iron + AA synergistically amplified cytotoxicity, increasing H2O2 and the mitochondrial permeability transition. Sauchinone protected hepatocytes from iron + AA-induced cytotoxicity, preventing the induction of mitochondrial dysfunction and apoptosis (EC50 = 1 μM), similar to the result using metformin. Sauchinone treatment activated LKB1, which led to AMPK activation: these events contributed to cell survival. Evidence of cytoprotection by LKB1 and AMPK activation was revealed in the reversal of sauchinone's restoration of the mitochondrial membrane potential by either dominant negative mutant AMPKα or chemical inhibitor. In conclusion, sauchinone protects the liver from toxicity induced by iron accumulation, and sauchinone's effects may be mediated by LKB1-dependent AMPK activation.",
author = "Kim, {Young Woo} and Lee, {Sung Min} and Shin, {Sang Mi} and Hwang, {Se Jin} and Brooks, {Janie S.} and Kang, {Hee Eun} and Lee, {Myung Gull} and Kim, {Sang Chan} and Kim, {Sang Geon}",
year = "2009",
month = "10",
day = "1",
doi = "10.1016/j.freeradbiomed.2009.07.018",
language = "English",
volume = "47",
pages = "1082--1092",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "7",

}

Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury. / Kim, Young Woo; Lee, Sung Min; Shin, Sang Mi; Hwang, Se Jin; Brooks, Janie S.; Kang, Hee Eun; Lee, Myung Gull; Kim, Sang Chan; Kim, Sang Geon.

In: Free Radical Biology and Medicine, Vol. 47, No. 7, 01.10.2009, p. 1082-1092.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury

AU - Kim, Young Woo

AU - Lee, Sung Min

AU - Shin, Sang Mi

AU - Hwang, Se Jin

AU - Brooks, Janie S.

AU - Kang, Hee Eun

AU - Lee, Myung Gull

AU - Kim, Sang Chan

AU - Kim, Sang Geon

PY - 2009/10/1

Y1 - 2009/10/1

N2 - Iron-overload disorders cause hepatocyte injury and inflammation by oxidative stress, possibly leading to liver fibrosis and hepatocellular carcinoma. This study investigated the efficacy of sauchinone, a bioactive lignan, in preventing iron-induced liver injury and explored the mechanism of sauchinone's activity. To create iron overload, mice were injected with phenylhydrazine, and the effects on hepatic iron and histopathology were assessed. Phenylhydrazine treatment promoted liver iron accumulation and ferritin expression, causing hepatocyte death and increased plasma arachidonic acid (AA). Sauchinone attenuated liver injury (EC50 = 10 mg/kg) and activated AMPK in mice. Treatment of hepatocytes with iron and AA simulated iron overload conditions: iron + AA synergistically amplified cytotoxicity, increasing H2O2 and the mitochondrial permeability transition. Sauchinone protected hepatocytes from iron + AA-induced cytotoxicity, preventing the induction of mitochondrial dysfunction and apoptosis (EC50 = 1 μM), similar to the result using metformin. Sauchinone treatment activated LKB1, which led to AMPK activation: these events contributed to cell survival. Evidence of cytoprotection by LKB1 and AMPK activation was revealed in the reversal of sauchinone's restoration of the mitochondrial membrane potential by either dominant negative mutant AMPKα or chemical inhibitor. In conclusion, sauchinone protects the liver from toxicity induced by iron accumulation, and sauchinone's effects may be mediated by LKB1-dependent AMPK activation.

AB - Iron-overload disorders cause hepatocyte injury and inflammation by oxidative stress, possibly leading to liver fibrosis and hepatocellular carcinoma. This study investigated the efficacy of sauchinone, a bioactive lignan, in preventing iron-induced liver injury and explored the mechanism of sauchinone's activity. To create iron overload, mice were injected with phenylhydrazine, and the effects on hepatic iron and histopathology were assessed. Phenylhydrazine treatment promoted liver iron accumulation and ferritin expression, causing hepatocyte death and increased plasma arachidonic acid (AA). Sauchinone attenuated liver injury (EC50 = 10 mg/kg) and activated AMPK in mice. Treatment of hepatocytes with iron and AA simulated iron overload conditions: iron + AA synergistically amplified cytotoxicity, increasing H2O2 and the mitochondrial permeability transition. Sauchinone protected hepatocytes from iron + AA-induced cytotoxicity, preventing the induction of mitochondrial dysfunction and apoptosis (EC50 = 1 μM), similar to the result using metformin. Sauchinone treatment activated LKB1, which led to AMPK activation: these events contributed to cell survival. Evidence of cytoprotection by LKB1 and AMPK activation was revealed in the reversal of sauchinone's restoration of the mitochondrial membrane potential by either dominant negative mutant AMPKα or chemical inhibitor. In conclusion, sauchinone protects the liver from toxicity induced by iron accumulation, and sauchinone's effects may be mediated by LKB1-dependent AMPK activation.

UR - http://www.scopus.com/inward/record.url?scp=69249240216&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69249240216&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2009.07.018

DO - 10.1016/j.freeradbiomed.2009.07.018

M3 - Article

C2 - 19616619

AN - SCOPUS:69249240216

VL - 47

SP - 1082

EP - 1092

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 7

ER -