Modulating propofol anesthesia and hepatotoxicity with monoterpene alcohols
Subtitle: molecular basis.
Published: 2004
Language: eng
Number of pages: 108
Description: Propofol is an intravenous anesthetic that is rapidly metabolized by glucuronidation and P450 catalyzed oxidation. The goal of this research was to determine whether monoterpene alcohols could be used to prolong the anesthetic effect of propofol by inhibiting propofol metabolism and modulate its hepatotoxicity; the molecular hepatotoxic mechanism of propofol in isolated hepatocytes. This research shows that most monoterpene alcohols administered intraperitoneally to mice prolonged the anesthetic effect (>3 times) of propofol. However, mouse plasma alanine aminotransferase levels also increased indicating that propofol was hepatotoxic. Propofol hepatotoxicity in vivo or hepatocyte cytotoxicity in vitro were increased by UGT inhibitors (-)-borneol or alpha-terpineol but may have been decreased by trans-sobrerol or P450 inhibitors. Moreover, hepatocyte cytotoxicity was also increased by catalase and quinone reductase inhibitors. These results suggest that 2,6-diisopropylbenzoquinone and phenoxy radicals contributed to propofol toxicity and monoterpene alcohols could be used to modulate propofol metabolism in vivo  and in vitro.
Notes: Adviser:  Peter J. O'Brien.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 42-06, page: 2178.

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