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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)2061-2069
Number of pages9
JournalMolecular Medicine Reports
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • Arachidonic acid
  • Baicalein
  • Carbon-centered radicals
  • D-galactosamine
  • Electron spin resonance
  • Hepatocytes
  • Hydroxyl radicals
  • Platelets

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Mechanism of free radical generation in platelets and primary hepatocytes: A novel electron spin resonance study'. Together they form a unique fingerprint.

  • Cite this