Cepharanthin, an alkaloid from Stephania cepharantha, inhibits increased pulmonary vascular permeability in an ovine model of sepsis.

Kazunori Murakami, Robert A. Cox, Hal K. Hawkins, Frank C. Schmalstieg, Roy W. McGuire, Jeffrey M. Jodoin, Lillian D. Traber, Daniel L. Traber

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Sepsis is a life-threatening event when it occurs in patients suffering from smoke inhalation injury. Pneumonia is one of the most frequent sources of infection in sepsis. Activated leukocytes likely play a role in the pathogenesis of sepsis. Cepharanthin is a biscoclaurine alkaloid that reportedly inhibits the activation of neutrophils. In this study, we investigated the effects of cephranthin on a post-smoke inhalation model of sepsis in sheep. Female sheep (n = 15) were surgically prepared for the study. After 5 days recovery from the operative procedures, tracheostomy was performed in all animals and 48 breaths of cotton smoke (<40 degrees C) were given via a modified bee smoker under halothane anesthesia. After smoke insufflation, Pseudomonas aeruginosa (5 x 109 cfu/kg) was instilled into the airway using a bronchoscope. All of the animals were mechanically ventilated with 100% O(2). Cepharanthin (1.3 mg/kg/h) was infused in five sheep continuously beginning 1 h after the insult and thereafter for the remainder of the 24-h study period. Control animals (n = 6) were treated with 5% dextrose as a vehicle control. Cepharanthin significantly attenuated changes in lung histology as well as in lung wet/dry weight ratio. An in vitro study revealed that cepharanthin inhibited the release of neutrophil elastase from isolated neutrophils stimulated with either formyl-methyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate with an IC(50) of 60 microM. Cepharanthin also inhibited the fMLP-induced increase in intracellular calcium levels of neutrophils. This result indicates cepharanthin inhibits protein kinase C or a more downstream signaling pathway in neutrophil activation. In conclusion, cepharanthin attenuates acute lung injury and septic shock after smoke inhalation in sheep.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalShock (Augusta, Ga.)
Volume20
Issue number1
StatePublished - Jul 2003

Fingerprint

Stephania
Capillary Permeability
Alkaloids
Sheep
Sepsis
Lung
Smoke
leucyl-phenylalanine
Neutrophil Activation
Inhalation
Neutrophils
Smoke Inhalation Injury
Bronchoscopes
Insufflation
Leukocyte Elastase
Acute Lung Injury
Tracheostomy
Bees
Operative Surgical Procedures
Tetradecanoylphorbol Acetate

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Murakami, K., Cox, R. A., Hawkins, H. K., Schmalstieg, F. C., McGuire, R. W., Jodoin, J. M., ... Traber, D. L. (2003). Cepharanthin, an alkaloid from Stephania cepharantha, inhibits increased pulmonary vascular permeability in an ovine model of sepsis. Shock (Augusta, Ga.), 20(1), 46-51.

Cepharanthin, an alkaloid from Stephania cepharantha, inhibits increased pulmonary vascular permeability in an ovine model of sepsis. / Murakami, Kazunori; Cox, Robert A.; Hawkins, Hal K.; Schmalstieg, Frank C.; McGuire, Roy W.; Jodoin, Jeffrey M.; Traber, Lillian D.; Traber, Daniel L.

In: Shock (Augusta, Ga.), Vol. 20, No. 1, 07.2003, p. 46-51.

Research output: Contribution to journalArticle

Murakami, K, Cox, RA, Hawkins, HK, Schmalstieg, FC, McGuire, RW, Jodoin, JM, Traber, LD & Traber, DL 2003, 'Cepharanthin, an alkaloid from Stephania cepharantha, inhibits increased pulmonary vascular permeability in an ovine model of sepsis.', Shock (Augusta, Ga.), vol. 20, no. 1, pp. 46-51.
Murakami, Kazunori ; Cox, Robert A. ; Hawkins, Hal K. ; Schmalstieg, Frank C. ; McGuire, Roy W. ; Jodoin, Jeffrey M. ; Traber, Lillian D. ; Traber, Daniel L. / Cepharanthin, an alkaloid from Stephania cepharantha, inhibits increased pulmonary vascular permeability in an ovine model of sepsis. In: Shock (Augusta, Ga.). 2003 ; Vol. 20, No. 1. pp. 46-51.
@article{0d66d4de6bf14d54a4581f9da7fc08ea,
title = "Cepharanthin, an alkaloid from Stephania cepharantha, inhibits increased pulmonary vascular permeability in an ovine model of sepsis.",
abstract = "Sepsis is a life-threatening event when it occurs in patients suffering from smoke inhalation injury. Pneumonia is one of the most frequent sources of infection in sepsis. Activated leukocytes likely play a role in the pathogenesis of sepsis. Cepharanthin is a biscoclaurine alkaloid that reportedly inhibits the activation of neutrophils. In this study, we investigated the effects of cephranthin on a post-smoke inhalation model of sepsis in sheep. Female sheep (n = 15) were surgically prepared for the study. After 5 days recovery from the operative procedures, tracheostomy was performed in all animals and 48 breaths of cotton smoke (<40 degrees C) were given via a modified bee smoker under halothane anesthesia. After smoke insufflation, Pseudomonas aeruginosa (5 x 109 cfu/kg) was instilled into the airway using a bronchoscope. All of the animals were mechanically ventilated with 100{\%} O(2). Cepharanthin (1.3 mg/kg/h) was infused in five sheep continuously beginning 1 h after the insult and thereafter for the remainder of the 24-h study period. Control animals (n = 6) were treated with 5{\%} dextrose as a vehicle control. Cepharanthin significantly attenuated changes in lung histology as well as in lung wet/dry weight ratio. An in vitro study revealed that cepharanthin inhibited the release of neutrophil elastase from isolated neutrophils stimulated with either formyl-methyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate with an IC(50) of 60 microM. Cepharanthin also inhibited the fMLP-induced increase in intracellular calcium levels of neutrophils. This result indicates cepharanthin inhibits protein kinase C or a more downstream signaling pathway in neutrophil activation. In conclusion, cepharanthin attenuates acute lung injury and septic shock after smoke inhalation in sheep.",
author = "Kazunori Murakami and Cox, {Robert A.} and Hawkins, {Hal K.} and Schmalstieg, {Frank C.} and McGuire, {Roy W.} and Jodoin, {Jeffrey M.} and Traber, {Lillian D.} and Traber, {Daniel L.}",
year = "2003",
month = "7",
language = "English (US)",
volume = "20",
pages = "46--51",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Cepharanthin, an alkaloid from Stephania cepharantha, inhibits increased pulmonary vascular permeability in an ovine model of sepsis.

AU - Murakami, Kazunori

AU - Cox, Robert A.

AU - Hawkins, Hal K.

AU - Schmalstieg, Frank C.

AU - McGuire, Roy W.

AU - Jodoin, Jeffrey M.

AU - Traber, Lillian D.

AU - Traber, Daniel L.

PY - 2003/7

Y1 - 2003/7

N2 - Sepsis is a life-threatening event when it occurs in patients suffering from smoke inhalation injury. Pneumonia is one of the most frequent sources of infection in sepsis. Activated leukocytes likely play a role in the pathogenesis of sepsis. Cepharanthin is a biscoclaurine alkaloid that reportedly inhibits the activation of neutrophils. In this study, we investigated the effects of cephranthin on a post-smoke inhalation model of sepsis in sheep. Female sheep (n = 15) were surgically prepared for the study. After 5 days recovery from the operative procedures, tracheostomy was performed in all animals and 48 breaths of cotton smoke (<40 degrees C) were given via a modified bee smoker under halothane anesthesia. After smoke insufflation, Pseudomonas aeruginosa (5 x 109 cfu/kg) was instilled into the airway using a bronchoscope. All of the animals were mechanically ventilated with 100% O(2). Cepharanthin (1.3 mg/kg/h) was infused in five sheep continuously beginning 1 h after the insult and thereafter for the remainder of the 24-h study period. Control animals (n = 6) were treated with 5% dextrose as a vehicle control. Cepharanthin significantly attenuated changes in lung histology as well as in lung wet/dry weight ratio. An in vitro study revealed that cepharanthin inhibited the release of neutrophil elastase from isolated neutrophils stimulated with either formyl-methyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate with an IC(50) of 60 microM. Cepharanthin also inhibited the fMLP-induced increase in intracellular calcium levels of neutrophils. This result indicates cepharanthin inhibits protein kinase C or a more downstream signaling pathway in neutrophil activation. In conclusion, cepharanthin attenuates acute lung injury and septic shock after smoke inhalation in sheep.

AB - Sepsis is a life-threatening event when it occurs in patients suffering from smoke inhalation injury. Pneumonia is one of the most frequent sources of infection in sepsis. Activated leukocytes likely play a role in the pathogenesis of sepsis. Cepharanthin is a biscoclaurine alkaloid that reportedly inhibits the activation of neutrophils. In this study, we investigated the effects of cephranthin on a post-smoke inhalation model of sepsis in sheep. Female sheep (n = 15) were surgically prepared for the study. After 5 days recovery from the operative procedures, tracheostomy was performed in all animals and 48 breaths of cotton smoke (<40 degrees C) were given via a modified bee smoker under halothane anesthesia. After smoke insufflation, Pseudomonas aeruginosa (5 x 109 cfu/kg) was instilled into the airway using a bronchoscope. All of the animals were mechanically ventilated with 100% O(2). Cepharanthin (1.3 mg/kg/h) was infused in five sheep continuously beginning 1 h after the insult and thereafter for the remainder of the 24-h study period. Control animals (n = 6) were treated with 5% dextrose as a vehicle control. Cepharanthin significantly attenuated changes in lung histology as well as in lung wet/dry weight ratio. An in vitro study revealed that cepharanthin inhibited the release of neutrophil elastase from isolated neutrophils stimulated with either formyl-methyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate with an IC(50) of 60 microM. Cepharanthin also inhibited the fMLP-induced increase in intracellular calcium levels of neutrophils. This result indicates cepharanthin inhibits protein kinase C or a more downstream signaling pathway in neutrophil activation. In conclusion, cepharanthin attenuates acute lung injury and septic shock after smoke inhalation in sheep.

UR - http://www.scopus.com/inward/record.url?scp=0042386664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042386664&partnerID=8YFLogxK

M3 - Article

VL - 20

SP - 46

EP - 51

JO - Shock

JF - Shock

SN - 1073-2322

IS - 1

ER -