Glucocorticoids attenuate septic acute kidney injury

Hye Min Choi, Sang Kyung Jo, Sung Hwan Kim, Jae Won Lee, Eunjung Cho, Young Youl Hyun, Jin Joo Cha, Young Sun Kang, Dae-Ryong Cha, Won Yong Cho, Hyoung Kyu Kim

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: The incidence and mortality of septic acute kidney injury (AKI) remains high, whereas our understanding of pathogenesis for septic AKI is still limited. Glucocorticoids (GCs) have been clinically recommended for treatment of septic shock and also have showed favorable effect on septic AKI in several animal experiments. The aim of this study is to investigate the pathophysiology of septic AKI and the effect of GCs on septic AKI. Methods: We induced septic AKI using cecal ligation and puncture (CLP) model in 8-10. wk-old male C57BL/6 mice. Saline or dexamethasone (2.5. mg/kg) dissolved in saline was administered after surgery. Hemodynamic, biochemical and histological changes were examined in a time-course manner. Results: CLP resulted in hyperdynamic warm shock with multiple organ dysfunction including AKI. Despite renal dysfunction, light microscopy showed scanty acute tubular necrosis and inflammation. Instead, CLP induced significant increase in apoptosis of the kidney and spleen cells. In addition, septic kidneys showed mitochondrial injury and alterations in Bcl2 family proteins in the renal tubular cells. Dexamethasone treatment attenuated renal dysfunction, but it was not associated with improvement of hemodynamic parameters. Dexamethasone-induced organ protective effect was associated with reduced mitochondrial injury with preserved cytochrome c oxidase and suppression of proapoptotic proteins as well as reduced cytokine release. Conclusions: Mitochondrial damage and subsequent apoptosis are thought to play important role in the development of septic AKI. GCs might be a useful therapeutic strategy for septic AKI by reducing mitochondrial damage and apoptosis.

Original languageEnglish
Pages (from-to)678-684
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume435
Issue number4
DOIs
Publication statusPublished - 2013 Jun 14

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Acute Kidney Injury
Dexamethasone
Glucocorticoids
Hemodynamics
Apoptosis
Kidney
Electron Transport Complex IV
Punctures
Surgery
Optical microscopy
Ligation
Animals
Proteins
Cytokines
Experiments
Wounds and Injuries
Septic Shock
Inbred C57BL Mouse
Microscopy
Shock

Keywords

  • Acute kidney injury
  • Apoptosis
  • Glucocorticoids
  • Mitochondria
  • Sepsis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Glucocorticoids attenuate septic acute kidney injury. / Choi, Hye Min; Jo, Sang Kyung; Kim, Sung Hwan; Lee, Jae Won; Cho, Eunjung; Hyun, Young Youl; Cha, Jin Joo; Kang, Young Sun; Cha, Dae-Ryong; Cho, Won Yong; Kim, Hyoung Kyu.

In: Biochemical and Biophysical Research Communications, Vol. 435, No. 4, 14.06.2013, p. 678-684.

Research output: Contribution to journalArticle

Choi, Hye Min ; Jo, Sang Kyung ; Kim, Sung Hwan ; Lee, Jae Won ; Cho, Eunjung ; Hyun, Young Youl ; Cha, Jin Joo ; Kang, Young Sun ; Cha, Dae-Ryong ; Cho, Won Yong ; Kim, Hyoung Kyu. / Glucocorticoids attenuate septic acute kidney injury. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 435, No. 4. pp. 678-684.
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AU - Kim, Sung Hwan

AU - Lee, Jae Won

AU - Cho, Eunjung

AU - Hyun, Young Youl

AU - Cha, Jin Joo

AU - Kang, Young Sun

AU - Cha, Dae-Ryong

AU - Cho, Won Yong

AU - Kim, Hyoung Kyu

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N2 - Background: The incidence and mortality of septic acute kidney injury (AKI) remains high, whereas our understanding of pathogenesis for septic AKI is still limited. Glucocorticoids (GCs) have been clinically recommended for treatment of septic shock and also have showed favorable effect on septic AKI in several animal experiments. The aim of this study is to investigate the pathophysiology of septic AKI and the effect of GCs on septic AKI. Methods: We induced septic AKI using cecal ligation and puncture (CLP) model in 8-10. wk-old male C57BL/6 mice. Saline or dexamethasone (2.5. mg/kg) dissolved in saline was administered after surgery. Hemodynamic, biochemical and histological changes were examined in a time-course manner. Results: CLP resulted in hyperdynamic warm shock with multiple organ dysfunction including AKI. Despite renal dysfunction, light microscopy showed scanty acute tubular necrosis and inflammation. Instead, CLP induced significant increase in apoptosis of the kidney and spleen cells. In addition, septic kidneys showed mitochondrial injury and alterations in Bcl2 family proteins in the renal tubular cells. Dexamethasone treatment attenuated renal dysfunction, but it was not associated with improvement of hemodynamic parameters. Dexamethasone-induced organ protective effect was associated with reduced mitochondrial injury with preserved cytochrome c oxidase and suppression of proapoptotic proteins as well as reduced cytokine release. Conclusions: Mitochondrial damage and subsequent apoptosis are thought to play important role in the development of septic AKI. GCs might be a useful therapeutic strategy for septic AKI by reducing mitochondrial damage and apoptosis.

AB - Background: The incidence and mortality of septic acute kidney injury (AKI) remains high, whereas our understanding of pathogenesis for septic AKI is still limited. Glucocorticoids (GCs) have been clinically recommended for treatment of septic shock and also have showed favorable effect on septic AKI in several animal experiments. The aim of this study is to investigate the pathophysiology of septic AKI and the effect of GCs on septic AKI. Methods: We induced septic AKI using cecal ligation and puncture (CLP) model in 8-10. wk-old male C57BL/6 mice. Saline or dexamethasone (2.5. mg/kg) dissolved in saline was administered after surgery. Hemodynamic, biochemical and histological changes were examined in a time-course manner. Results: CLP resulted in hyperdynamic warm shock with multiple organ dysfunction including AKI. Despite renal dysfunction, light microscopy showed scanty acute tubular necrosis and inflammation. Instead, CLP induced significant increase in apoptosis of the kidney and spleen cells. In addition, septic kidneys showed mitochondrial injury and alterations in Bcl2 family proteins in the renal tubular cells. Dexamethasone treatment attenuated renal dysfunction, but it was not associated with improvement of hemodynamic parameters. Dexamethasone-induced organ protective effect was associated with reduced mitochondrial injury with preserved cytochrome c oxidase and suppression of proapoptotic proteins as well as reduced cytokine release. Conclusions: Mitochondrial damage and subsequent apoptosis are thought to play important role in the development of septic AKI. GCs might be a useful therapeutic strategy for septic AKI by reducing mitochondrial damage and apoptosis.

KW - Acute kidney injury

KW - Apoptosis

KW - Glucocorticoids

KW - Mitochondria

KW - Sepsis

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