Role of mitochondrial complex I and protective effect of CoQ10 supplementation in propofol induced cytotoxicity
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- 作者：Christian Bergamini ; Noah Moruzzi…
- 关键词：Propofol ; Complex I ; Mitochondria ; Anaesthesia ; Oxygen consumption
- 刊名：Journal of Bioenergetics and Biomembranes
- 出版年：2016
- 出版时间：August 2016
- 年：2016
- 卷：48
- 期：4
- 页码：413-423
- 全文大小：886 KB
- 刊物类别：Chemistry and Materials Science
- 刊物主题：Chemistry
Bioorganic Chemistry
Biochemistry
Animal Anatomy, Morphology and Histology
Animal Biochemistry
Organic Chemistry - 出版者：Springer New York
- ISSN：1573-6881
- 卷排序：48
文摘
Propofol (2,6-diisopropylphenol) is an anaesthetic widely used for human sedation. Due to its intrinsic antioxidant properties, rapid induction of anaesthesia and fast recovery, it is employed in paediatric anaesthesia and in the intensive care of premature infants. Recent studies have pointed out that exposure to anaesthesia in the early stage of life might be responsible of long-lasting cognitive impairment. The apoptotic neurodegeneration induced by general anaesthetics (GA) involves mitochondrial impairment due to the inhibition of the OXPHOS machinery. In the present work, we aim to identify the main mitochondrial respiratory chain target of propofol toxicity and to evaluate the possible protective effect of CoQ10 supplementation. The propofol effect on the mitochondrial functionality was assayed in isolated mitochondria and in two cell lines (HeLa and T67) by measuring oxygen consumption rate. The protective effect of CoQ10 was assessed by measuring cells viability, NADH-oxidase activity and ATP/ADP ratio in cells treated with propofol. Our results show that propofol reduces cellular oxygen consumption rate acting mainly on mitochondrial Complex I. The kinetic analysis of Complex I inhibition indicates that propofol interferes with the Q module acting as a non-competitive inhibitor with higher affinity for the free form of the enzyme. Cells supplemented with CoQ10 are more resistant to propofol toxicity. Propofol exposure induces cellular damages due to mitochondrial impairment. The site of propofol inhibition on Complex I is the Q module. CoQ10 supplementation protects cells against the loss of energy suggesting its possible therapeutic role to minimizing the detrimental effects of general anaesthesia.