Oral administration of cilostazol improves survival rate after rat liver ischemia/reperfusion injury

Taku Fujii, Hideaki Obara, Kentaro Matsubara, Naoki Fujimura, Hiroshi Yagi, Taizo Hibi, Yuta Abe, Minoru Kitago, Masahiro Shinoda, Osamu Itano, Minoru Tanabe, Yohei Masugi, Michiie Sakamoto, Yuukou Kitagawa

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Abstract

Background Cilostazol is a type III phosphodiesterase inhibitor used to treat the symptoms of intermittent claudication. Recent studies have shown that cilostazol decreases ischemia/reperfusion (I/R) injury in several organs. Materials and methods We evaluated the effects of cilostazol in a rat model of liver I/R injury. Thirty male Wistar rats with liver I/R injury were divided into a cilostazol or saline (control) group (n = 15 each). Each rat was orally administered cilostazol or saline for 3 d before I/R injury. Liver I/R injury was induced via 1 h of warm ischemia of the median and left lateral liver lobes, followed by 3 h of reperfusion. The rats were then euthanized. Serum aspartate aminotransferase, alanine aminotransferase, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels were measured. The Mann–Whitney U test was used to compare the differences between the treatment groups. Histologic examination was performed on the liver tissues. We also conducted a survival study to confirm the effect of cilostazol on the mortality rate in rats. For the survival study, a liver I/R injury model with an ischemia time of 1.5 h was used, and the rats were observed for 1 wk. Results Serum aspartate aminotransferase, alanine aminotransferase, IL-1β, and IL-6 levels were significantly lower in the cilostazol group than in the saline group. Treatment with cilostazol significantly improved pathological findings associated with liver I/R injury and increased survival rate compared to that in controls. Conclusions Cilostazol reduced mortality and alleviated the effects of liver I/R injury in Wistar rats.

Original languageEnglish
Pages (from-to)207-214
Number of pages8
JournalJournal of Surgical Research
Volume213
DOIs
Publication statusPublished - 2017 Jun 1

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Reperfusion Injury
Oral Administration
Survival Rate
Liver
Aspartate Aminotransferases
Alanine Transaminase
Interleukin-1
Wistar Rats
Interleukin-6
cilostazol
Warm Ischemia
Intermittent Claudication
Phosphodiesterase Inhibitors
Mortality
Serum
Reperfusion
Ischemia
Tumor Necrosis Factor-alpha
Control Groups
Therapeutics

Keywords

  • Alanine aminotransferase
  • Aspartate aminotransferase
  • Cilostazol
  • Hepatocyte injury
  • Partial ischemia/reperfusion injury
  • Phosphodiesterase III inhibitor

ASJC Scopus subject areas

  • Surgery

Cite this

@article{5bd5accc24294c64827a78b70eb1adbd,
title = "Oral administration of cilostazol improves survival rate after rat liver ischemia/reperfusion injury",
abstract = "Background Cilostazol is a type III phosphodiesterase inhibitor used to treat the symptoms of intermittent claudication. Recent studies have shown that cilostazol decreases ischemia/reperfusion (I/R) injury in several organs. Materials and methods We evaluated the effects of cilostazol in a rat model of liver I/R injury. Thirty male Wistar rats with liver I/R injury were divided into a cilostazol or saline (control) group (n = 15 each). Each rat was orally administered cilostazol or saline for 3 d before I/R injury. Liver I/R injury was induced via 1 h of warm ischemia of the median and left lateral liver lobes, followed by 3 h of reperfusion. The rats were then euthanized. Serum aspartate aminotransferase, alanine aminotransferase, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels were measured. The Mann–Whitney U test was used to compare the differences between the treatment groups. Histologic examination was performed on the liver tissues. We also conducted a survival study to confirm the effect of cilostazol on the mortality rate in rats. For the survival study, a liver I/R injury model with an ischemia time of 1.5 h was used, and the rats were observed for 1 wk. Results Serum aspartate aminotransferase, alanine aminotransferase, IL-1β, and IL-6 levels were significantly lower in the cilostazol group than in the saline group. Treatment with cilostazol significantly improved pathological findings associated with liver I/R injury and increased survival rate compared to that in controls. Conclusions Cilostazol reduced mortality and alleviated the effects of liver I/R injury in Wistar rats.",
keywords = "Alanine aminotransferase, Aspartate aminotransferase, Cilostazol, Hepatocyte injury, Partial ischemia/reperfusion injury, Phosphodiesterase III inhibitor",
author = "Taku Fujii and Hideaki Obara and Kentaro Matsubara and Naoki Fujimura and Hiroshi Yagi and Taizo Hibi and Yuta Abe and Minoru Kitago and Masahiro Shinoda and Osamu Itano and Minoru Tanabe and Yohei Masugi and Michiie Sakamoto and Yuukou Kitagawa",
year = "2017",
month = "6",
day = "1",
doi = "10.1016/j.jss.2017.02.020",
language = "English",
volume = "213",
pages = "207--214",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Oral administration of cilostazol improves survival rate after rat liver ischemia/reperfusion injury

AU - Fujii, Taku

AU - Obara, Hideaki

AU - Matsubara, Kentaro

AU - Fujimura, Naoki

AU - Yagi, Hiroshi

AU - Hibi, Taizo

AU - Abe, Yuta

AU - Kitago, Minoru

AU - Shinoda, Masahiro

AU - Itano, Osamu

AU - Tanabe, Minoru

AU - Masugi, Yohei

AU - Sakamoto, Michiie

AU - Kitagawa, Yuukou

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background Cilostazol is a type III phosphodiesterase inhibitor used to treat the symptoms of intermittent claudication. Recent studies have shown that cilostazol decreases ischemia/reperfusion (I/R) injury in several organs. Materials and methods We evaluated the effects of cilostazol in a rat model of liver I/R injury. Thirty male Wistar rats with liver I/R injury were divided into a cilostazol or saline (control) group (n = 15 each). Each rat was orally administered cilostazol or saline for 3 d before I/R injury. Liver I/R injury was induced via 1 h of warm ischemia of the median and left lateral liver lobes, followed by 3 h of reperfusion. The rats were then euthanized. Serum aspartate aminotransferase, alanine aminotransferase, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels were measured. The Mann–Whitney U test was used to compare the differences between the treatment groups. Histologic examination was performed on the liver tissues. We also conducted a survival study to confirm the effect of cilostazol on the mortality rate in rats. For the survival study, a liver I/R injury model with an ischemia time of 1.5 h was used, and the rats were observed for 1 wk. Results Serum aspartate aminotransferase, alanine aminotransferase, IL-1β, and IL-6 levels were significantly lower in the cilostazol group than in the saline group. Treatment with cilostazol significantly improved pathological findings associated with liver I/R injury and increased survival rate compared to that in controls. Conclusions Cilostazol reduced mortality and alleviated the effects of liver I/R injury in Wistar rats.

AB - Background Cilostazol is a type III phosphodiesterase inhibitor used to treat the symptoms of intermittent claudication. Recent studies have shown that cilostazol decreases ischemia/reperfusion (I/R) injury in several organs. Materials and methods We evaluated the effects of cilostazol in a rat model of liver I/R injury. Thirty male Wistar rats with liver I/R injury were divided into a cilostazol or saline (control) group (n = 15 each). Each rat was orally administered cilostazol or saline for 3 d before I/R injury. Liver I/R injury was induced via 1 h of warm ischemia of the median and left lateral liver lobes, followed by 3 h of reperfusion. The rats were then euthanized. Serum aspartate aminotransferase, alanine aminotransferase, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels were measured. The Mann–Whitney U test was used to compare the differences between the treatment groups. Histologic examination was performed on the liver tissues. We also conducted a survival study to confirm the effect of cilostazol on the mortality rate in rats. For the survival study, a liver I/R injury model with an ischemia time of 1.5 h was used, and the rats were observed for 1 wk. Results Serum aspartate aminotransferase, alanine aminotransferase, IL-1β, and IL-6 levels were significantly lower in the cilostazol group than in the saline group. Treatment with cilostazol significantly improved pathological findings associated with liver I/R injury and increased survival rate compared to that in controls. Conclusions Cilostazol reduced mortality and alleviated the effects of liver I/R injury in Wistar rats.

KW - Alanine aminotransferase

KW - Aspartate aminotransferase

KW - Cilostazol

KW - Hepatocyte injury

KW - Partial ischemia/reperfusion injury

KW - Phosphodiesterase III inhibitor

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U2 - 10.1016/j.jss.2017.02.020

DO - 10.1016/j.jss.2017.02.020

M3 - Article

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JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

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