Copyright © 2004, European Society of Cardiology
Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via a prooxidant mechanism
Department of Biochemistry, The Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
* Corresponding author. Tel.: +852 2609 6874; fax: +852 2603 7732. Email address: mary-waye{at}cuhk.edu.hk
Objectives: Baicalin and its aglycone baicalein are the major flavonoid components of the root of Scutellaria baicalensis. Recent studies have shown that they can attenuate oxidative stress in various in vitro models as they possess potent antioxidant activities. This study investigated alternative protective mechanisms of baicalein in a cardiomyocyte model.
Methods: Neonatal rat cardiomyocytes pretreated with the test compound were subjected to hypoxia/reoxygenation. The extent of cellular damage was accessed by the amount of released lactate dehydrogenase
Results: Pretreatment with baicalein up to 10 µM reduced lactate dehydrogenase release significantly (P<0.001), while pretreatment with baicalin up to 100 µM was ineffective. The cardioprotective effect of baicalein is not due to its antioxidant effect, because an adverse effect rather than a protective effect was observed when baicalein was present during hypoxia. Cotreatment with N-acetylcysteine attenuated the protective effect of baicalein and concomitantly increased intracellular reactive oxygen species level and the cytotoxic effect of baicalein, but N-acetylcysteine alone did not have such effects. In addition, cotreatment with catalase, but not superoxide dismutase or mannitol, reversed the cardioprotective effect of baicalein, suggesting the involvement of hydrogen peroxide in the cardioprotective mechanism. The NAD(P)H:quinone oxidoreductase inhibitors dicoumarol and chrysin also abolished the cardioprotective effect of baicalein. While pretreatment with baicalein did not increase antioxidant enzyme activities, it alleviated calcium accumulation in cardiomyocytes undergoing simulated ischemia.
Conclusion: These results highlight the important role of hydrogen peroxide produced during the auto-oxidation of baicalein in the cardioprotective effect of baicalein.
KEYWORDS baicalein; Prooxidant; Hydrogen peroxide; Cardioprotection; Hypoxia; Reoxygenation
1 These authors contributed equally to the work.
Time for primary review 28 days
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