Effect of pyruvate on rat heart thiol status during ischemia and hypoxia followed by reperfusion.
Ischemia or hypoxia followed by reperfusion determine a large release of glutathione from isolated and perfused rat heart. The effects of glucose and/or pyruvate administered during ischemia/reperfusion or hypoxia/reperfusion on the release of cytosolic and mitochondrial glutathione are compared. During ischemia, mitochondrial glutathione is released from the mitochondrion to the cytosol forming a unique pool that leaks out to the interstitial space. Reperfusion causes a large release of total glutathione, particularly from cytosol. Total sulfhydryl groups do not undergo modifications after ischemia, while they appear to decrease upon reperfusion. Pyruvate, which protects the heart by inducing a large recovery of the contractile activity after ischemia, markedly prevents the loss of glutathione. Also total sulfhydryl groups of mitochondria do not undergo significant variation upon ischemia and reperfusion in the presence of pyruvate. During hypoxia, in the absence of glucose, glutathione is mainly lost from the cytosol, while the mitochondrial pool appears to be preserved; in hypoxia, at variance with the ischemic conditions, pyruvate does not show any beneficial effect. The action of pyruvate appears to be multifactorial and its effects are discussed by considering its action on the hydrogen peroxide breakdown, protection of pyruvate dehydrogenase, anaerobic production of ATP and diminution of the intracellular concentration of inorganic phosphate.
Rigobello
M P
MP
Centro Studio Fisiologia Mitocondriale (CNR), Università di Padova, Italy.
Bindoli
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D000818:Animals; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D010084:Oxidation-Reduction; D011773:Pyruvates / Q000494:pharmacology*; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D011773:Pyruvates; D013438:Sulfhydryl Compounds; D019289:Pyruvic Acid; D005978:Glutathione