Time-dependent enhancement in mitochondrial glutathione status and ATP generation capacity by schisandrin B treatment decreases the susceptibility of rat hearts to ischemia-reperfusion injury.

Abstract

In the present study, we examined the time-dependent changes in the mitochondrial glutathione status and ATP generation capacity in the myocardium as well as the susceptibility of the myocardium to ischemia-reperfusion (IR) injury in female Sprague Dawley rats treated with a single pharmacological dose (1.2 mmol/kg) of schisandrin B (Sch B). Sch B treatment produced a time-dependent enhancement in myocardial mitochondrial glutathione status, as evidenced by increases in myocardial mitochondrial reduced glutathione (GSH) level and activities of glutathione reductase, Se-glutathione peroxidase (GPX) and glutathione S-transferases, with the response reaching maximum at 48 h post-dosing and then declining gradually to the control level at 96 h post-dosing. The enhancement of mitochondrial glutathione status was associated with an increase in myocardial ATP generation capacity, with the value peaking at 72 h post-dosing. These beneficial effects of Sch B on the myocardium was paralleled by a time-dependent decrease in the susceptibility to IR injury, with the maximum protection demonstrable at 48 h post-dosing. The cardioprotection was associated with increases in myocardial GSH level and activities of glutathione antioxidant enzymes (except for GPX whose activity was suppressed) as well as tissue ATP level/ATP generation capacity. The results suggest that Sch B treatment can precondition the myocardium by enhancing the mitochondrial glutathione status and ATP generation capacity, thereby protecting against IR injury.

• Authors: Po Yee Chiu, Kam Ming Ko
• Journal: BioFactors (Oxford, England) (Biofactors) Vol. 19 Issue 1-2 Pg. 43-51 ( 2003) ISSN: 0951-6433 [Print] Netherlands
• PMID: 14757976 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Cyclooctanes
• Lignans
• Polycyclic Compounds
• schizandrin B
• Adenosine Triphosphate
• Glutathione

Topics

• Adenosine Triphosphate (biosynthesis)
• Animals
• Antioxidants (chemistry, pharmacology)
• Cyclooctanes (chemistry, pharmacology)
• Female
• Glutathione (metabolism)
• Heart (drug effects)
• Lignans (chemistry, pharmacology)
• Mitochondria, Heart (drug effects, metabolism)
• Myocardium (metabolism)
• Polycyclic Compounds (chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (prevention & control)
• Time Factors