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Effect of selected drugs on mitochondrial metabolism in an in vitro model of human skeletal muscle
Krajčová, Adéla ; Anděl, Michal (advisor) ; Kieslichová, Eva (referee) ; Houštěk, Josef (referee)
Introduction: Increasing number of reports reflect that mitochondrial dysfunction can be induced by some of the commonly used drugs and can play a key role in the development of their adverse effects. One of these drugs is a phenol derivative propofol. Propofol is an intravenous, fast and short-acting hypnotic agent, routinely used either for induction and maintenance of anaesthesia during surgery, or for sedation in intensive care units. Propofol infusion syndrome (PRIS) is a rare, but serious adverse effect of the drug with a very high mortality. Typical features of the syndrome include metabolic acidosis, arrhythmias, ECG changes that are similar to those of Brugada syndrome, hypertriglyceridemia, fever, hepatomegaly, rhabdomyolysis, cardiac and/or renal failure. The risk of the syndrome increases with raising dose and duration of propofol administration (˃48 hours). The mechanism of the syndrome is still unknown: pilot studies performed on animal models are suggestive of its mitochondrial origin. In the first part of the study, we performed the analysis of 153 published case reports and all experimental studies related to PRIS. Another aim of the study was to test hypothesis of propofol- induced mitochondrial damage by in vitro exposure of human skeletal muscle-derived cells to a range of...
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Effect of selected drugs on mitochondrial metabolism in an in vitro model of human skeletal muscle
Krajčová, Adéla ; Anděl, Michal (advisor) ; Kieslichová, Eva (referee) ; Houštěk, Josef (referee)
Introduction: Increasing number of reports reflect that mitochondrial dysfunction can be induced by some of the commonly used drugs and can play a key role in the development of their adverse effects. One of these drugs is a phenol derivative propofol. Propofol is an intravenous, fast and short-acting hypnotic agent, routinely used either for induction and maintenance of anaesthesia during surgery, or for sedation in intensive care units. Propofol infusion syndrome (PRIS) is a rare, but serious adverse effect of the drug with a very high mortality. Typical features of the syndrome include metabolic acidosis, arrhythmias, ECG changes that are similar to those of Brugada syndrome, hypertriglyceridemia, fever, hepatomegaly, rhabdomyolysis, cardiac and/or renal failure. The risk of the syndrome increases with raising dose and duration of propofol administration (˃48 hours). The mechanism of the syndrome is still unknown: pilot studies performed on animal models are suggestive of its mitochondrial origin. In the first part of the study, we performed the analysis of 153 published case reports and all experimental studies related to PRIS. Another aim of the study was to test hypothesis of propofol- induced mitochondrial damage by in vitro exposure of human skeletal muscle-derived cells to a range of...
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