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Combined effect of propofol and GSNO on oxidative phosphorylation of isolated rat liver mitochondria
R Stevanato1, F Momo, M Marian
1Department of Physical Chemistry, University of Venice, Italy.
Abstract:
Isolated rat liver mitochondria have been treated with the general anaesthetic propofol (2,6-diisopropylphenol, 200 microM) and the physiological NO donor nitrosoglutathione (GSNO, 200 or 250 microM). The efficiency of the oxidative phosphorylation has been evaluated by measuring the respiration and ATP synthesis rates and the behavior of transmembrane electrical potential. In mitochondria energized by succinate, the simultaneous presence of both propofol and GSNO gives rise to a synergic action in affecting the resting and the ADP-stimulated respiration, the respiratory control ratio, the ATP synthesis, and the formation and utilization of the electrochemical transmembrane potential.
Insights
Propofol and nitrosoglutathione (GSNO) synergistically impair mitochondrial function. This combined effect significantly impacts respiration, ATP synthesis, and the transmembrane potential in isolated rat liver mitochondria.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Mitochondria are crucial for cellular energy production via oxidative phosphorylation.
- Propofol is a widely used anesthetic agent with known effects on cellular processes.
- Nitric oxide (NO) plays diverse physiological roles, and its donors can influence mitochondrial function.
Purpose of the Study:
- To investigate the combined effects of propofol and nitrosoglutathione (GSNO) on isolated rat liver mitochondria.
- To evaluate the impact of these agents on oxidative phosphorylation efficiency.
Main Methods:
- Isolated rat liver mitochondria were treated with propofol and GSNO.
- Respiration rates, ATP synthesis, and transmembrane electrical potential were measured.
- Mitochondria were energized using succinate.
Main Results:
- Propofol and GSNO exhibited a synergistic effect on mitochondrial function.
- Both resting and ADP-stimulated respiration were significantly affected.
- ATP synthesis, respiratory control ratio, and transmembrane potential dynamics were altered.
Conclusions:
- The simultaneous administration of propofol and GSNO leads to a synergistic impairment of mitochondrial oxidative phosphorylation.
- This interaction affects key parameters of mitochondrial energy metabolism and membrane potential.
- These findings highlight potential complex interactions between anesthetics and endogenous signaling molecules within mitochondria.
