Propofol attenuates Kupffer cell activation during hypoxia-reoxygenation.
OBJECTIVE
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)-alpha mRNA, and KC viability were measured in response to hypoxia-reoxygenation following pretreatment with propofol 0.5 and 5 microg.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-alpha 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-alpha 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.


CONCLUSIONS
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.
Sung
Eon-Gi
EG
Kupffer Cell Research Group, Yeungnam University College of Medicine, Daemyung-Dong, Nam-Gu, Daegu, Korea 705-035.
Jee
Daelim
D
Song
In-Hwan
IH
Kim
Hee-Sun
HS
Bae
Jae Hoon
JH
Park
Se-Hun
SH
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000860:Hypoxia / Q000503:physiopathology*; D007728:Kupffer Cells / Q000187:drug effects*; D008297:Male; D010100:Oxygen / Q000097:blood*; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018686:Anesthetics, Intravenous; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen; D002118:Calcium; D015742:Propofol