PROPOFOL PRESERVES THE VIABILITY OF ISOLATED RAT HEPATOCYTE SUSPENSIONS UNDER AN OXIDANT STRESS

The purpose of this study was to investigate whether propofol protects rat hepatocyte suspensions against an oxidant attack by a free radica l generator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). Rat hepatocyte suspensions (2 x 10(6) cells/mL) were prepared using Segle n's collagenase perfusion technique. Suspensions were treated with AAP H (50 mM) alone, propofol (28 mu M) plus AAPH, or, in a separate exper iment, with either AAPH alone or 10% intralipid (0.5 mu L/mL) plus AAP H. Each experiment had untreated control suspensions. Cell viability w as measured at 1, 2, and 3 h using the trypan blue exclusion test and expressed as a percentage of the initial number of viable cells. Cells taken from control at time 0 h and each experimental group at 1 h fro m five separate hepatocyte preparations were examined by electron micr oscopy. Control cell viability deceased with time. The addition of AAP H significantly reduced viability compared with control (P < 0.0001); pretreatment with propofol significantly attenuated this effect at 1 h (P 0.0008), but 10% intralipid had no effect. Electron microscopy rev ealed structural changes in cell membranes that could have accounted f or the inability to exclude trypan blue. In conclusion, a 28-mu M conc entration of propofol protects rat hepatocytes from an oxidant stress sufficient to cause cell death at 1 h. Implications: Oxidants contribu te to tissue injury in a variety of situations. We have shown that the anesthetic propofol improves survival of liver cells exposed to oxida nt injury at blood concentrations achieved in anesthetized patients. T hese effects may be relevant during transplantation and critical illne ss.