Effects of nitrosopropofol on mitochondrial energy-converting system.
Nitrosopropofol (NOPR) is a relatively stable compound obtained from the reaction between the general anesthetic 2,6 diisopropylphenol (propofol) and nitrosoglutathione (GSNO) and bearing a more acidic phenol group than propofol. It interfered with mitochondrial energetic metabolism in a concentration-dependent manner. Concentrations as high as 100 or 200 microM disrupted both oxidative phosphorylation and electron transport. Low concentrations of NOPR (50 microM) markedly slowed down the electron transport rate which was insensitive both to ADP and uncoupler stimulation and spontaneously gradually stopped. Consequently, both the transmembrane potential production and the ATP synthesis system were affected. In the presence of 10 or 20 microM NOPR, mitochondria respired but showed a worsening of the respiratory control and produced a transmembrane potential useful to respond to a phosphorylation pulse, but were not able to restore it. These results were consistent with ATP synthesis and swelling experiments. NOPR was effective at concentrations lower than those required by the combination of propofol and GSNO, suggesting that mitochondria might be able to catalyze the reaction between GSNO and propofol and that the resulting metabolite was more active on mitochondrial membrane structure than the parent compounds. Although the details of the process are yet unknown, the mechanism presented may be of potential relevance to rationalize the pathophysiological effects of propofol.
Stevanato
Roberto
R
Department of Physical Chemistry, University of Venice, Venice, Italy
Momo
Federico
F
Marian
Michela
M
Rigobello
Maria Pia
MP
Bindoli
Alberto
A
Bragadin
Marcantonio
M
Vincenti
Ezio
E
Scutari
Guido
G
D000777:Anesthetics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004734:Energy Metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D015742:Propofol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000777:Anesthetics; C466059:nitrosopropofol; D015742:Propofol