MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia

Goro Takahashi, Masahiro Sakurai, Koji Abe, Yasuto Itoyama, Koichi Tabayashi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background Paraplegia is a serious complication of operations on the thoracic and thoracoabdominal aorta. To investigate the mechanism by which motor neurons are damaged during these operations, we have reported a rabbit model of spinal cord ischemia. We also tested whether a free radical scavenger MCI-186 that is useful for treating ischemic damage in the brain can protect against ischemic spinal cord damage. Methods Fifteen minutes of ischemia was induced, then MCI-186 or vehicle was injected intravenously. Cell damage was analyzed by observing the function of the lower limbs and by counting the number of motor neurons. To investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage, we observed the immunoreactivity of 8-hydroxy-2'-deoxyguanosine as an oxidative DNA damage marker and redox effector as a DNA repair marker. Results In sham control, 8-hydroxy-2'-deoxyguanosine was not observed, and the nuclear expression of redox effector was observed. In vehicle injection group (group I), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was observed at 1 and 2 days after reperfusion. The nuclear expression of redox effector was observed at 8 hours and 1 day, and disappeared at 2 days after transient ischemia. In MCI-186 injection group (group M), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was not observed, and redox effector was observed at 8 hours and 1 and 2 days. Conclusions These results suggest that redox effector decreased in motor neurons after transient ischemia and this reduction preceded oxidative DNA damage. MCI-186 works as a radical scavenger and reduced oxidative DNA damage, so redox effector did not disappear. MCI-186 could be a strong candidate for a use as a therapeutic agent in the treatment of ischemic spinal cord injury.

Original languageEnglish
Pages (from-to)602-607
Number of pages6
JournalAnnals of Thoracic Surgery
Volume78
Issue number2
DOIs
Publication statusPublished - Aug 2004

Fingerprint

DNA Repair
Oxidation-Reduction
Spinal Cord
Ischemia
Rabbits
Motor Neurons
DNA Damage
Genetic Markers
Spinal Cord Ischemia
Free Radical Scavengers
Injections
Paraplegia
Thoracic Aorta
Spinal Cord Injuries
Reperfusion
phenylmethylpyrazolone
Lower Extremity
8-oxo-7-hydrodeoxyguanosine
Brain
Therapeutics

Keywords

  • 19

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia. / Takahashi, Goro; Sakurai, Masahiro; Abe, Koji; Itoyama, Yasuto; Tabayashi, Koichi.

In: Annals of Thoracic Surgery, Vol. 78, No. 2, 08.2004, p. 602-607.

Research output: Contribution to journalArticle

Takahashi, Goro ; Sakurai, Masahiro ; Abe, Koji ; Itoyama, Yasuto ; Tabayashi, Koichi. / MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia. In: Annals of Thoracic Surgery. 2004 ; Vol. 78, No. 2. pp. 602-607.
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