Heme Oxygenase, Ginkgo Biloba Extract and its Terpenoids Protect Myocytes Against Oxidative Injury

Abstract

A number of pharmacological approaches to protect against myocardial damage during ischemia reperfusion events (e.g. β-blockers, calcium antagonists, nitrates, and free radical scavengers) have met with limited success. For example, administration of exogenous antioxidants during and after myocardial ischemial-reperfusion were not sufficient to protect intracellular targets against reactive oxidant species, because exogenous antioxidants are membrane impermeable and cannot gain access to intracellular sites of free radical production and reaction. Development of other novel approaches to enhance endogenous cardioprotective mechanisms to minimize myocardial damage during ischemial-reperfusion is currently a major area of investigation. Since its first description by Murry et al. manipulation of myocardial protection via “ischemic preconditioning (I/P)” has been revealed to trigger endogenous protective mechanisms that increase cardiomyocytes resistance to oxidative stress (Murry et al., 1986; Parratt, 1994). Two classes of cellular protectants, heat shock proteins (HSPs) and endogenous anti-oxidant enzymes (Yellon and Baxter, 1995), have been postulated to participate in this I/P induced cardioprotection. Accumulation of HSP70 in myocytes was associated with an enhancement structural stabilization in cardiac tissue. It was shown that transfecting cells with HSP70 gene conferred cyto-protection against hydrogen peroxide, hypoxia/reoxygenation injury (Chong et al., 1998; Plumier et al., 1995). Overexpression of HSP70 dramatically reduced infarct size in hearts of transgenic HSP70 mouse model (Marber et al., 1995).