title: 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.affiliation: Department of Biochemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Po Yee
authors.initials: PY
authors.lastname: Chiu
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D034242:Cyclooctanes / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D000255:Adenosine Triphosphate; D005978:Glutathione