Blockade of Kupffer cells by gadolinium chloride reduces lipid peroxidation and protects liver from ischemia/reperfusion injury.
OBJECTIVE
The implication of lipid peroxidation in the inhibitory effect of GdCl3 (gadolinium chloride) on Kupffer cells activation has not been extensively investigated. The aim of this study was to examine the effect of GdCl3 inhibition of Kupffer cells activation on lipid peroxidation after severe total hepatic ischemia/reperfusion.


METHODS
Male Wistar rats (n = 40) were randomly divided into a sham-operation group, a control ischemia/reperfusion group, and two ischemia/reperfusion groups pretreated with GdCl3 (10 mg and 20 mg/kg bw intravenously, 48 and 24 h prior to operation). Following 60 min of total hepatic ischemia and 120 min of reperfusion, the rats were sacrificed, and liver samples were taken for determination of malondialdehyde and light microscopy examination. Blood samples were also taken for assay of aspartate and alanine transaminase. Additional animals (n = 60) were followed up for a 7-day survival rate determination.


RESULTS
Ischemia/reperfusion decreased the survival rate to 13.3%, increased (p < 0.001) the levels of aspartate and alanine transaminase in serum to 2387 +/- 75 and 2157 +/- 87 IU/L, respectively, and increased (p < 0.001) malondialdehyde levels in liver to 1.609 +/- 0.096 nmoles/g compared with 1.164 +/- 0.060 in the sham operation group. Pretreatment with GdCl3 increased the survival rate to 60%, and decreased (p < 0.001) the levels of aspartate transaminase in serum to 1549 +/- 66 and 1496 +/- 55 IU/L, the levels of alanine transaminase in serum to 1302 +/- 48 and 1305 +/- 63 IU/L, and the levels of malondialdehyde in liver to 1.132 +/- 0.034 and 1.149 +/- 0.57 nmoles/g for the lower and the higher doses of GdCl3, respectively. Histological examination showed protection of liver parenchyma in the animals treated with GdCl3.


CONCLUSIONS
Experimental data suggest that GdCl3 inhibition of Kupffer cells activation protects liver from ischemia/reperfusion injury by a mechanism that reduces lipid peroxidation.
Fifth Surgical Department, Aristotle University, Hospital Hippokration, Konstantinoupoleos 49, 54642 Thessaloniki, Greece. dgiak@auth.gr
D E
DE
Giakoustidis
S
S
Iliadis
D
D
Tsantilas
G
G
Papageorgiou
N
N
Kontos
E
E
Kostopoulou
N A
NA
Botsoglou
T
T
Gerasimidis
A
A
Dimitriadou
D000818:Animals; D005682:Gadolinium / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects* / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control
D005682:Gadolinium; C038958:gadolinium chloride