Propofol preserves the viability of isolated rat hepatocyte suspensions under an oxidant stress

Abstract

The purpose of this study was to investigate whether propofol protects rat hepatocyte suspensions against an oxidant attack by a free radical generator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). Rat hepatocyte suspensions (2 x 10(6) cells/mL) were prepared using Seglen's collagenase perfusion technique. Suspensions were treated with AAPH (50 mM) alone, propofol (28 microM) plus AAPH, or, in a separate experiment, with either AAPH alone or 10% intralipid (0.5 microL/mL) plus AAPH. Each experiment had untreated control suspensions. Cell viability was 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 from five separate hepatocyte preparations were examined by electron microscopy. Control cell viability decreased with time. The addition of AAPH 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 revealed structural changes in cell membranes that could have accounted for the inability to exclude trypan blue. In conclusion, a 28-microM concentration of propofol protects rat hepatocytes from an oxidant stress sufficient to cause cell death at 1 h.

Implications: Oxidants contribute to tissue injury in a variety of situations. We have shown that the anesthetic propofol improves survival of liver cells exposed to oxidant injury at blood concentrations achieved in anesthetized patients. These effects may be relevant during transplantation and critical illness.