Abstract

BACKGROUND: Oxidation and inflammation caused by lower limb ischemia-reperfusion (I/R) readily induce lung injury. We elucidated whether cepharanthine, a potent antioxidative and anti-inflammatory drug, can mitigate lung injury induced by lower limb I/R. Role of heme oxygenase 1 (HO-1) was also investigated.

MATERIALS AND METHODS: Adult male Sprague-Dawley rats were randomized to receive I/R, I/R plus cepharanthine, or I/R plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP; n = 12 in each group). Sham control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 24 h.

RESULTS: Rats receiving I/R had significant increases in concentrations of nitric oxide, malondialdehyde (lipid peroxidation marker), and inflammatory molecules (including interleukin 6, macrophage inflammatory protein 2, and prostaglandin E2) in plasma, and the lungs, indicating that I/R caused significant oxidation and inflammation in rats. Rats receiving I/R also had significant increases in concentration of phosphorylated inhibitor-κB, indicating that I/R caused significant nuclear factor κB activation. Assays of arterial blood gas, biochemistry, and histopathology confirmed that I/R-induced significant lung injury in rats. Cepharanthine significantly reduced the oxidation, inflammation, nuclear factor κB activation, and lung injury induced by I/R. Of note, cepharanthine significantly enhanced pulmonary HO-1 expression after I/R. Moreover, these previously mentioned effects of cepharanthine were partially reversed by inhibiting the activity of HO-1.

CONCLUSIONS: Cepharanthine mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve its effects on reducing oxidation and inflammation. The mechanisms may also involve enhancing HO-1 expression.

Original languageEnglish
Pages (from-to)647-656
Number of pages10
JournalThe Journal of surgical research
Volume199
Issue number2
DOIs
Publication statusPublished - Dec 1 2015

Fingerprint

Lung Injury
Reperfusion
Lower Extremity
Ischemia
Heme Oxygenase-1
Inflammation
cepharanthine
Chemokine CXCL2
Lung
Tourniquets
Rubber
Thigh
Malondialdehyde
Dinoprostone
Biochemistry
Lipid Peroxidation
Sprague Dawley Rats
Interleukin-6
Nitric Oxide
Anti-Inflammatory Agents

Keywords

  • Chemokine
  • Cytokine
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Surgery

Cite this

Cepharanthine mitigates lung injury in lower limb ischemia-reperfusion. / Kao, Ming Chang; Yang, Chen Hsien; Chou, Wei Chih; Sheu, Joen Rong; Huang, Chun Jen.

In: The Journal of surgical research, Vol. 199, No. 2, 01.12.2015, p. 647-656.

Research output: Contribution to journalArticle

Kao, Ming Chang ; Yang, Chen Hsien ; Chou, Wei Chih ; Sheu, Joen Rong ; Huang, Chun Jen. / Cepharanthine mitigates lung injury in lower limb ischemia-reperfusion. In: The Journal of surgical research. 2015 ; Vol. 199, No. 2. pp. 647-656.
@article{380094fd5e014d1aba37a10db8892d2e,
title = "Cepharanthine mitigates lung injury in lower limb ischemia-reperfusion",
abstract = "BACKGROUND: Oxidation and inflammation caused by lower limb ischemia-reperfusion (I/R) readily induce lung injury. We elucidated whether cepharanthine, a potent antioxidative and anti-inflammatory drug, can mitigate lung injury induced by lower limb I/R. Role of heme oxygenase 1 (HO-1) was also investigated.MATERIALS AND METHODS: Adult male Sprague-Dawley rats were randomized to receive I/R, I/R plus cepharanthine, or I/R plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP; n = 12 in each group). Sham control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 24 h.RESULTS: Rats receiving I/R had significant increases in concentrations of nitric oxide, malondialdehyde (lipid peroxidation marker), and inflammatory molecules (including interleukin 6, macrophage inflammatory protein 2, and prostaglandin E2) in plasma, and the lungs, indicating that I/R caused significant oxidation and inflammation in rats. Rats receiving I/R also had significant increases in concentration of phosphorylated inhibitor-κB, indicating that I/R caused significant nuclear factor κB activation. Assays of arterial blood gas, biochemistry, and histopathology confirmed that I/R-induced significant lung injury in rats. Cepharanthine significantly reduced the oxidation, inflammation, nuclear factor κB activation, and lung injury induced by I/R. Of note, cepharanthine significantly enhanced pulmonary HO-1 expression after I/R. Moreover, these previously mentioned effects of cepharanthine were partially reversed by inhibiting the activity of HO-1.CONCLUSIONS: Cepharanthine mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve its effects on reducing oxidation and inflammation. The mechanisms may also involve enhancing HO-1 expression.",
keywords = "Chemokine, Cytokine, Inflammation, Oxidative stress",
author = "Kao, {Ming Chang} and Yang, {Chen Hsien} and Chou, {Wei Chih} and Sheu, {Joen Rong} and Huang, {Chun Jen}",
year = "2015",
month = "12",
day = "1",
doi = "10.1016/j.jss.2015.06.041",
language = "English",
volume = "199",
pages = "647--656",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Cepharanthine mitigates lung injury in lower limb ischemia-reperfusion

AU - Kao, Ming Chang

AU - Yang, Chen Hsien

AU - Chou, Wei Chih

AU - Sheu, Joen Rong

AU - Huang, Chun Jen

PY - 2015/12/1

Y1 - 2015/12/1

N2 - BACKGROUND: Oxidation and inflammation caused by lower limb ischemia-reperfusion (I/R) readily induce lung injury. We elucidated whether cepharanthine, a potent antioxidative and anti-inflammatory drug, can mitigate lung injury induced by lower limb I/R. Role of heme oxygenase 1 (HO-1) was also investigated.MATERIALS AND METHODS: Adult male Sprague-Dawley rats were randomized to receive I/R, I/R plus cepharanthine, or I/R plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP; n = 12 in each group). Sham control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 24 h.RESULTS: Rats receiving I/R had significant increases in concentrations of nitric oxide, malondialdehyde (lipid peroxidation marker), and inflammatory molecules (including interleukin 6, macrophage inflammatory protein 2, and prostaglandin E2) in plasma, and the lungs, indicating that I/R caused significant oxidation and inflammation in rats. Rats receiving I/R also had significant increases in concentration of phosphorylated inhibitor-κB, indicating that I/R caused significant nuclear factor κB activation. Assays of arterial blood gas, biochemistry, and histopathology confirmed that I/R-induced significant lung injury in rats. Cepharanthine significantly reduced the oxidation, inflammation, nuclear factor κB activation, and lung injury induced by I/R. Of note, cepharanthine significantly enhanced pulmonary HO-1 expression after I/R. Moreover, these previously mentioned effects of cepharanthine were partially reversed by inhibiting the activity of HO-1.CONCLUSIONS: Cepharanthine mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve its effects on reducing oxidation and inflammation. The mechanisms may also involve enhancing HO-1 expression.

AB - BACKGROUND: Oxidation and inflammation caused by lower limb ischemia-reperfusion (I/R) readily induce lung injury. We elucidated whether cepharanthine, a potent antioxidative and anti-inflammatory drug, can mitigate lung injury induced by lower limb I/R. Role of heme oxygenase 1 (HO-1) was also investigated.MATERIALS AND METHODS: Adult male Sprague-Dawley rats were randomized to receive I/R, I/R plus cepharanthine, or I/R plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP; n = 12 in each group). Sham control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 24 h.RESULTS: Rats receiving I/R had significant increases in concentrations of nitric oxide, malondialdehyde (lipid peroxidation marker), and inflammatory molecules (including interleukin 6, macrophage inflammatory protein 2, and prostaglandin E2) in plasma, and the lungs, indicating that I/R caused significant oxidation and inflammation in rats. Rats receiving I/R also had significant increases in concentration of phosphorylated inhibitor-κB, indicating that I/R caused significant nuclear factor κB activation. Assays of arterial blood gas, biochemistry, and histopathology confirmed that I/R-induced significant lung injury in rats. Cepharanthine significantly reduced the oxidation, inflammation, nuclear factor κB activation, and lung injury induced by I/R. Of note, cepharanthine significantly enhanced pulmonary HO-1 expression after I/R. Moreover, these previously mentioned effects of cepharanthine were partially reversed by inhibiting the activity of HO-1.CONCLUSIONS: Cepharanthine mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve its effects on reducing oxidation and inflammation. The mechanisms may also involve enhancing HO-1 expression.

KW - Chemokine

KW - Cytokine

KW - Inflammation

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=85027941924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027941924&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2015.06.041

DO - 10.1016/j.jss.2015.06.041

M3 - Article

VL - 199

SP - 647

EP - 656

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -