Glutathione metabolism in non-ischemic and postischemic rat hearts in response to an exogenous prooxidant.
The objective of the present study was to determine whether mild ischemia hampers the use of tissue concentration of glutathione disulfide (GSSG) and release of GSSG as indices of oxidative stress in postischemic hearts. To this end, the response of the glutathione redox cycle to the prooxidant cumene hydroperoxide (CumOOH) was compared in non-ischemic and postischemic rat hearts perfused in vitro. Perfusion of non-ischemic and postischemic hearts with CumOOH (20-25 microM) for 10 min followed by 20 min of perfusion without CumOOH resulted in similar changes in tissue concentration of GSSG, and similar patterns of GSSG release. The similar response in tissue concentration of GSSG is consistent with the finding that mild ischemia did not affect the formation and reduction of GSSG. While release of GSSG from non-ischemic hearts was solely due to active transport of GSSG, release of GSSG from postischemic hearts was due to both active transport of GSSG and aspecific leakage of GSSG. In conclusion, tissue concentration of GSSG can be reliably used to investigate oxidative stress in postischemic hearts. However, the occurrence of aspecific leakage of GSSG, which is not indicative of oxidative stress, renders release of GSSG from postischemic hearts an unreliable index of oxidative stress.
Verbunt
R J
RJ
Department of Cardiology, University Hospital, Leiden, The Netherlands.
Van der Laarse
A
A
D000818:Animals; D001555:Benzene Derivatives / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D001555:Benzene Derivatives; D016877:Oxidants; D005978:Glutathione; C007164:cumene hydroperoxide; D019803:Glutathione Disulfide