Propofol attenuates Kupffer cell activation during hypoxia-reoxygenation

Abstract

Purpose: We undertook a study to determine whether propofol may attenuate Kupffer cell (KC) activation, thus protecting the cells against hypoxia-reoxygenation injury through the modulation of intracellular calcium ([Ca2+]i). Methods: [Ca2+]i, the expression of tumour necrosis factor (TNF)-α mRNA, and KC viability were measured in response to hypoxia-reoxygenation following pretreatment with propofol 0.5 and 5 μg·mL-1 (Groups P1 and P2, respectively) or without propofol (Group HRC). KCs were isolated and cultured from male Sprague-Dawley rats. KCs were incubated under an atmosphere of hypoxia (95% N2 + 5% CO2) for 60 min with subsequent 120 min reoxygenation (95% air + 5% CO2). [Ca2+]i for the first 12 min after reoxygenation, TNF-α mRNA, and KC viability at the end of reoxygenation in groups P1 and P2 were compared with those of HRC. Results: The increase of [Ca2+]i from the baseline was attenuated in P1 (96.6 ± 6.9%) and P2 (96.1 ± 5.4%) compared with HRC (143.8 ± 11.5%), (P < 0.001), with no difference between P1 and P2. The expression of TNF-α mRNA increased only in HRC during hypoxia-reoxygenation. KC viability increased in P1 (97.5 ± 2.6%) and P2 (94.6 ± 2.9%), compared with HRC (89.9 ± 1.4%), (P < 0.005), with no difference between P1 and P2. Conclusion: The results indicate that propofol attenuates KC activation and protects KC from hypoxia-reoxygenation injury at clinically relevant concentrations. This attenuation seems to result from inhibition of [Ca2+]i increase in KC.