Mechanism of free radical generation in platelets and primary hepatocytes

A novel electron spin resonance study

Chiun Lang Wang, Po Sheng Yang, Jeng Ting Tsao, Thanasekaran Jayakumar, Meng Jiy Wang, Joen Rong Sheu, Duen Suey Chou

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Oxygen free radicals have been implicated in the pathogenesis of toxic liver injury and are thought to be involved in cardiac dysfunction in the cirrhotic heart. Therefore, direct evidence for the electron spin resonance (ESR) detection of how D-galactosamine (GalN), an established experimental hepatotoxic substance, induced free radicals formation in platelets and primary hepatocytes is presented in the present study. ESR results demonstrated that GalN induced hydroxyl radicals (OH') in a resting human platelet suspension; however, radicals were not produced in a cell free Fenton reaction system. The GalN-induced OH' formation was significantly inhibited by the cyclooxygenase (COX) inhibitor indomethasin, though it was not affected by the lipoxygenase (LOX) or cytochrome P450 inhibitors, AA861 and 1-aminobenzotriazole (ABT), in platelets. In addition, the present study demonstrated that baicalein induced semiquinone free radicals in platelets, which were significantly reduced by the COX inhibitor without affecting the formed OH'. In the mouse primary hepatocytes, the formation of arachidonic acid (AA) induced carbon-centered radicals that were concentration dependently enhanced by GalN. These radicals were inhibited by AA861, though not affected by indomethasin or ABT. In addition, GalN did not induce platelet aggregation prior to or following collagen pretreatment in human platelets. The results of the present study indicated that GalN and baicalein may induce OH' by COX and LOX in human platelets. GalN also potentiated AA induced carbon-centered radicals in hepatocytes via cytochrome P450. The present study presented the role of free radicals in the pathophysiological association between platelets and hepatocytes.
原文英語
頁(從 - 到)2061-2069
頁數9
期刊Molecular Medicine Reports
17
發行號1
DOIs
出版狀態已發佈 - 一月 1 2018

指紋

Electron Spin Resonance Spectroscopy
Platelets
Free Radicals
Paramagnetic resonance
Hepatocytes
Blood Platelets
Lipoxygenase
Cyclooxygenase Inhibitors
Arachidonic Acid
Cytochrome P-450 Enzyme System
Carbon
Galactosamine
Poisons
Prostaglandin-Endoperoxide Synthases
Platelet Aggregation
Hydroxyl Radical
Reactive Oxygen Species
Suspensions
Liver
Collagen

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

引用此文

Mechanism of free radical generation in platelets and primary hepatocytes : A novel electron spin resonance study. / Wang, Chiun Lang; Yang, Po Sheng; Tsao, Jeng Ting; Jayakumar, Thanasekaran; Wang, Meng Jiy; Sheu, Joen Rong; Chou, Duen Suey.

於: Molecular Medicine Reports, 卷 17, 編號 1, 01.01.2018, p. 2061-2069.

研究成果: 雜誌貢獻文章

Wang, Chiun Lang ; Yang, Po Sheng ; Tsao, Jeng Ting ; Jayakumar, Thanasekaran ; Wang, Meng Jiy ; Sheu, Joen Rong ; Chou, Duen Suey. / Mechanism of free radical generation in platelets and primary hepatocytes : A novel electron spin resonance study. 於: Molecular Medicine Reports. 2018 ; 卷 17, 編號 1. 頁 2061-2069.
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abstract = "Oxygen free radicals have been implicated in the pathogenesis of toxic liver injury and are thought to be involved in cardiac dysfunction in the cirrhotic heart. Therefore, direct evidence for the electron spin resonance (ESR) detection of how D-galactosamine (GalN), an established experimental hepatotoxic substance, induced free radicals formation in platelets and primary hepatocytes is presented in the present study. ESR results demonstrated that GalN induced hydroxyl radicals (OH') in a resting human platelet suspension; however, radicals were not produced in a cell free Fenton reaction system. The GalN-induced OH' formation was significantly inhibited by the cyclooxygenase (COX) inhibitor indomethasin, though it was not affected by the lipoxygenase (LOX) or cytochrome P450 inhibitors, AA861 and 1-aminobenzotriazole (ABT), in platelets. In addition, the present study demonstrated that baicalein induced semiquinone free radicals in platelets, which were significantly reduced by the COX inhibitor without affecting the formed OH'. In the mouse primary hepatocytes, the formation of arachidonic acid (AA) induced carbon-centered radicals that were concentration dependently enhanced by GalN. These radicals were inhibited by AA861, though not affected by indomethasin or ABT. In addition, GalN did not induce platelet aggregation prior to or following collagen pretreatment in human platelets. The results of the present study indicated that GalN and baicalein may induce OH' by COX and LOX in human platelets. GalN also potentiated AA induced carbon-centered radicals in hepatocytes via cytochrome P450. The present study presented the role of free radicals in the pathophysiological association between platelets and hepatocytes.",
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T2 - A novel electron spin resonance study

AU - Wang, Chiun Lang

AU - Yang, Po Sheng

AU - Tsao, Jeng Ting

AU - Jayakumar, Thanasekaran

AU - Wang, Meng Jiy

AU - Sheu, Joen Rong

AU - Chou, Duen Suey

PY - 2018/1/1

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N2 - Oxygen free radicals have been implicated in the pathogenesis of toxic liver injury and are thought to be involved in cardiac dysfunction in the cirrhotic heart. Therefore, direct evidence for the electron spin resonance (ESR) detection of how D-galactosamine (GalN), an established experimental hepatotoxic substance, induced free radicals formation in platelets and primary hepatocytes is presented in the present study. ESR results demonstrated that GalN induced hydroxyl radicals (OH') in a resting human platelet suspension; however, radicals were not produced in a cell free Fenton reaction system. The GalN-induced OH' formation was significantly inhibited by the cyclooxygenase (COX) inhibitor indomethasin, though it was not affected by the lipoxygenase (LOX) or cytochrome P450 inhibitors, AA861 and 1-aminobenzotriazole (ABT), in platelets. In addition, the present study demonstrated that baicalein induced semiquinone free radicals in platelets, which were significantly reduced by the COX inhibitor without affecting the formed OH'. In the mouse primary hepatocytes, the formation of arachidonic acid (AA) induced carbon-centered radicals that were concentration dependently enhanced by GalN. These radicals were inhibited by AA861, though not affected by indomethasin or ABT. In addition, GalN did not induce platelet aggregation prior to or following collagen pretreatment in human platelets. The results of the present study indicated that GalN and baicalein may induce OH' by COX and LOX in human platelets. GalN also potentiated AA induced carbon-centered radicals in hepatocytes via cytochrome P450. The present study presented the role of free radicals in the pathophysiological association between platelets and hepatocytes.

AB - Oxygen free radicals have been implicated in the pathogenesis of toxic liver injury and are thought to be involved in cardiac dysfunction in the cirrhotic heart. Therefore, direct evidence for the electron spin resonance (ESR) detection of how D-galactosamine (GalN), an established experimental hepatotoxic substance, induced free radicals formation in platelets and primary hepatocytes is presented in the present study. ESR results demonstrated that GalN induced hydroxyl radicals (OH') in a resting human platelet suspension; however, radicals were not produced in a cell free Fenton reaction system. The GalN-induced OH' formation was significantly inhibited by the cyclooxygenase (COX) inhibitor indomethasin, though it was not affected by the lipoxygenase (LOX) or cytochrome P450 inhibitors, AA861 and 1-aminobenzotriazole (ABT), in platelets. In addition, the present study demonstrated that baicalein induced semiquinone free radicals in platelets, which were significantly reduced by the COX inhibitor without affecting the formed OH'. In the mouse primary hepatocytes, the formation of arachidonic acid (AA) induced carbon-centered radicals that were concentration dependently enhanced by GalN. These radicals were inhibited by AA861, though not affected by indomethasin or ABT. In addition, GalN did not induce platelet aggregation prior to or following collagen pretreatment in human platelets. The results of the present study indicated that GalN and baicalein may induce OH' by COX and LOX in human platelets. GalN also potentiated AA induced carbon-centered radicals in hepatocytes via cytochrome P450. The present study presented the role of free radicals in the pathophysiological association between platelets and hepatocytes.

KW - Arachidonic acid

KW - Baicalein

KW - Carbon-centered radicals

KW - D-galactosamine

KW - Electron spin resonance

KW - Hepatocytes

KW - Hydroxyl radicals

KW - Platelets

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U2 - 10.3892/mmr.2017.8058

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JF - Molecular Medicine Reports

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