Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Cytotoxic Effect of Free Radical on Rat Primary Astrocytes

자유라디칼이 백서의 뇌별아교세포에 미치는 독성작용

  • Jang, Hyuk (Department of Neurology, School of Medicine, Wonkwang University) ;
  • Kim, Myung-Sunny (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Park, Hyun-Young (Department of Neurology, School of Medicine, Wonkwang University) ;
  • Kim, Yo-Sik (Department of Neurology, School of Medicine, Wonkwang University) ;
  • Cho, Kwang-Ho (Department of Neurology, School of Medicine, Wonkwang University) ;
  • Chung, Hun-Taeg (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Park, Rae-Kil (Department of Microbiology, School of Medicine, Wonkwang University)
  • 장혁 (원광대학교 의과대학 신경과학교실) ;
  • 김명선 (원광대학교 의과대학 미생물학교실) ;
  • 박현영 (원광대학교 의과대학 신경과학교실) ;
  • 김요식 (원광대학교 의과대학 신경과학교실) ;
  • 조광호 (원광대학교 의과대학 신경과학교실) ;
  • 정헌택 (원광대학교 의과대학 미생물학교실) ;
  • 박래길 (원광대학교 의과대학 미생물학교실)
  • Published : 2000.03.01
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Abstract

Astrocytes generate free radicals including nitric oxide (NO) and reactive oxygen intermediates(ROI) which in turn play roles in the pathogenesis of degenerative diseases and sclerotic changes of the brain. This study was designed to evaluate the mechanism that free radicals contribute to the cytotoxicty of rat neonatal primary astrocytes. Treatment with NO donors alone including soldium nitroprusside(SNP), S-nitrosoglucathinoe (GSNO), and S-nitroso-n-acetylpenicillamine (SNAP) showed a little effect on the death of rat neonatal primary astrocytes, whereas SNP markedly induced the death of RAW 264.7 cells. ROI inculding H2O2 and O2 donor also slightly induced the death of rat primary astrocytes. However, 3-morpholinosydnonimine(SIN-1), a donor of peroxynitrite (ONOO), which is a reactive compound of NO with superoxide, significantly decreased the viability of rat primary astrocytes in a dose-dependent manner. Cells were retarded in outgrowth of viability of cellular processes with cell shrinkage and detachment from culture dishes. Hoechst staining demonstrated that SIN-1-induced cell death might be due to an apoptosis which was characterized by nuclear condensation and fragmentation. SIN-1-induced apoptosis was prevented by the pretreatment with superoxide dismutase (SOD) and catalase in rat primary astorocytes. Furthermore, prevention of the generation of reduced glutathione (GSH) by DL-buthionine-[S, R]-sulfoximine (BSO) aggravated the cytotoxic effects of SNP, benzene triol, and SIN-1 in rat primary astrocytes. Taken together, it is suggested that peroxynitrite may be a major effector of apoptosis and cellular antioxidant system is important for cell survival in rat prima교 astrocytes.

Keywords

References

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