Dose-dependent protective effect of propofol against mitochondrial dysfunction in ischaemic/reperfused rat heart: role of cardiolipin.
OBJECTIVE
Ischaemia damages to the cardiac mitochondria by increasing generation of reactive oxygen species (ROS) and peroxidation of cardiolipin. The inhibited mitochondrial function leads to the cardiac injury during reperfusion. Propofol (2, 6-diisopropylphenol), an intravenous anaesthetic, has been shown to decrease cardiac ischaemia and reperfusion injury. In the present study, we propose that propofol protects mitochondrial function and decreases cardiac injury by prevention of cardiolipin peroxidation during ischaemia and reperfusion.


METHODS
After isolation of mitochondria from isolated rat heart perfused on a Langendorff model, various mitochondrial bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, H(2)O(2) production, complex I and III activity as well as the degree of lipid peroxidation and cardiolipin content. The action of propofol was also explored in isolated mitochondria. And the effect of cardiolipin was evaluated by fusing cardiolipin liposome with mitochondria.


RESULTS
Propofol treatment had strong dose-dependent protection attenuating these parameters alterations in reperfused rat heart and isolated mitochondria. Additionally, cardiolipin treatment had the same protective effect, compared with propofol treatment at high concentration.


CONCLUSIONS
The protective effect of propofol appears to be due, at least in part, as a chemical uncoupler, to the interruption of the vicious circle of ROS-cardiolipin-complexes of the respiratory chain-ROS through preserving the content and integrity of cardiolipin molecules by ROS attack. These findings may provide an explanation for some of the factors responsible for cardioprotection and one approach exploring an available antioxidant.
Shao
H
H
Xuzhou Medical College, Jiangsu Province, People's Republic of China.
Li
J
J
Zhou
Y
Y
Ge
Z
Z
Fan
J
J
Shao
Z
Z
Zeng
Y
Y
D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D002308:Cardiolipins; D006993:Hypnotics and Sedatives; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D015742:Propofol