A free radical scavenger, edaravone, attenuates steatosis and cell death via reducing inflammatory cytokine production in rat acute liver injury

Nobuhiro Nakamoto, Shinichiro Tada, Kaori Kameyama, Kumi Kitamura, Satoshi Kurita, Yoshimasa Saito, Hidetsugu Saito, Hiromasa Ishii

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background/Aims: Reactive oxygen radicals play an important role in various forms of liver injury. In this study, we evaluated the efficacy of edaravone, a newly synthesized free radical scavenger, in its clinical dosage on an experimental model of acute liver injury in rats. Methods: The clinical dose of edaravone (3 mg/kg) was intravenously administered immediately and 3h after intraperitoneal administration of carbon tetrachloride (CCl4) in rats. Histological evaluation including apoptosis and cytokine profiles were examined. Results: Fatty degeneration and necrosis with marked elevation of serum alanine aminotransferase and lactate dehydrogenase levels developed after CCl4 administration were significantly reduced by edaravone. In addition, the apoptotic index assessed by TUNEL method was significantly lowered in the edaravone treated group. Serum and liver transcription levels of interleukin-6, tumor necrosis factor-α, interleukin-4, and interleukin-10 were increased following CCl4 administration, and they were attenuated by edaravone treatment. The formation of malondialdehyde, 4-hydroxynonenal adduct and one of the markers for oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, was also inhibited by edaravone treatment. Conclusion: Edaravone has a remarkable protective effect on acute liver injury caused by oxygen radicals through not only attenuating the membrane lipid peroxidation, but also inhibiting the production of inflammatory cytokines. We theorize that edaravone may have a clinical benefit in the treatment of various liver injuries.

Original languageEnglish
Pages (from-to)849-859
Number of pages11
JournalFree Radical Research
Volume37
Issue number8
DOIs
Publication statusPublished - 2003 Aug 1

Fingerprint

Free Radical Scavengers
Cell death
Liver
Rats
Cell Death
Cytokines
Wounds and Injuries
Reactive Oxygen Species
phenylmethylpyrazolone
Carbon Tetrachloride
In Situ Nick-End Labeling
Transcription
Membrane Lipids
Malondialdehyde
Serum
Alanine Transaminase
L-Lactate Dehydrogenase
Interleukin-4
Interleukin-10
Lipid Peroxidation

Keywords

  • Acute liver injury
  • Carbon tetrachloride
  • Edaravone
  • Free radicals
  • Inflammatory cytokine
  • Lipid peroxidation

ASJC Scopus subject areas

  • Biochemistry

Cite this

A free radical scavenger, edaravone, attenuates steatosis and cell death via reducing inflammatory cytokine production in rat acute liver injury. / Nakamoto, Nobuhiro; Tada, Shinichiro; Kameyama, Kaori; Kitamura, Kumi; Kurita, Satoshi; Saito, Yoshimasa; Saito, Hidetsugu; Ishii, Hiromasa.

In: Free Radical Research, Vol. 37, No. 8, 01.08.2003, p. 849-859.

Research output: Contribution to journalArticle

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N2 - Background/Aims: Reactive oxygen radicals play an important role in various forms of liver injury. In this study, we evaluated the efficacy of edaravone, a newly synthesized free radical scavenger, in its clinical dosage on an experimental model of acute liver injury in rats. Methods: The clinical dose of edaravone (3 mg/kg) was intravenously administered immediately and 3h after intraperitoneal administration of carbon tetrachloride (CCl4) in rats. Histological evaluation including apoptosis and cytokine profiles were examined. Results: Fatty degeneration and necrosis with marked elevation of serum alanine aminotransferase and lactate dehydrogenase levels developed after CCl4 administration were significantly reduced by edaravone. In addition, the apoptotic index assessed by TUNEL method was significantly lowered in the edaravone treated group. Serum and liver transcription levels of interleukin-6, tumor necrosis factor-α, interleukin-4, and interleukin-10 were increased following CCl4 administration, and they were attenuated by edaravone treatment. The formation of malondialdehyde, 4-hydroxynonenal adduct and one of the markers for oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, was also inhibited by edaravone treatment. Conclusion: Edaravone has a remarkable protective effect on acute liver injury caused by oxygen radicals through not only attenuating the membrane lipid peroxidation, but also inhibiting the production of inflammatory cytokines. We theorize that edaravone may have a clinical benefit in the treatment of various liver injuries.

AB - Background/Aims: Reactive oxygen radicals play an important role in various forms of liver injury. In this study, we evaluated the efficacy of edaravone, a newly synthesized free radical scavenger, in its clinical dosage on an experimental model of acute liver injury in rats. Methods: The clinical dose of edaravone (3 mg/kg) was intravenously administered immediately and 3h after intraperitoneal administration of carbon tetrachloride (CCl4) in rats. Histological evaluation including apoptosis and cytokine profiles were examined. Results: Fatty degeneration and necrosis with marked elevation of serum alanine aminotransferase and lactate dehydrogenase levels developed after CCl4 administration were significantly reduced by edaravone. In addition, the apoptotic index assessed by TUNEL method was significantly lowered in the edaravone treated group. Serum and liver transcription levels of interleukin-6, tumor necrosis factor-α, interleukin-4, and interleukin-10 were increased following CCl4 administration, and they were attenuated by edaravone treatment. The formation of malondialdehyde, 4-hydroxynonenal adduct and one of the markers for oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, was also inhibited by edaravone treatment. Conclusion: Edaravone has a remarkable protective effect on acute liver injury caused by oxygen radicals through not only attenuating the membrane lipid peroxidation, but also inhibiting the production of inflammatory cytokines. We theorize that edaravone may have a clinical benefit in the treatment of various liver injuries.

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