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Dose-dependent protective effect of propofol against mitochondrial dysfunction in ischaemic/reperfused rat heart: role of cardiolipin.
- Source :
- British Journal of Pharmacology; Apr2008, Vol. 153 Issue 8, p1641-1649, 9p, 1 Black and White Photograph, 1 Chart, 7 Graphs
- Publication Year :
- 2008
-
Abstract
- <bold>Background and Purpose: </bold>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.<bold>Experimental Approach: </bold>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.<bold>Key Results: </bold>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.<bold>Conclusions and Implications: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- MITOCHONDRIAL pathology
ANTIGEN-antibody reactions
CARDIOLIPIN
ISCHEMIA
INTRAVENOUS therapy
LABORATORY rats
REPERFUSION injury
PROPOFOL
IN vitro studies
RESEARCH
ANIMAL experimentation
RESEARCH methodology
MEDICAL cooperation
EVALUATION research
MYOCARDIAL reperfusion complications
RATS
MITOCHONDRIA
COMPARATIVE studies
DOSE-effect relationship in pharmacology
PHOSPHOLIPIDS
REACTIVE oxygen species
HYDROGEN peroxide
LIPID peroxidation (Biology)
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 153
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31630934
- Full Text :
- https://doi.org/10.1038/bjp.2008.45