Protective effect of gadolinium chloride on early warm ischemia/reperfusion injury in rat bile duct during liver transplantation.
BACKGROUND
Activation of Kupffer cell (KC) is acknowledged as a key event in the initiation and perpetuation of bile duct warm ischemia/reperfusion injury. The inhibitory effect of gadolinium chloride (GdCl(3)) on KC activation shows potential as a protective intervention in liver injury, but there is less research with regard to bile duct injury.


METHODS
Sixty-five male Sprague-Dawley rats (200-250 g) were randomly divided into three experimental groups: a sham group (n = 15), a control group (n = 25), and a GdCl(3) group (n = 25). Specimen was collected at 0.5, 2, 6, 12 and 24 h after operation. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL) of serum were measured. Tumor necrosis factor-α (TNF-α), Capase-3 activity and soluble Fas (sFas) were detected. The pathologic changes of bile duct were observed. Immunochemistry for bile duct Fas was performed. Apoptosis of bile duct cells was evaluated by the terminal UDP nick end labeling assay.


RESULTS
GdCl(3) significantly decreased the levels of ALT, ALP and TBIL at 2, 6, 12, and 24 h, and increased serum sFas at 2, 6 and 12 h (P<0.05). TNF-α was lower in the GdCl(3) group than in the control group at 2, 6, 12 and 24 h (P<0.05). Preadministration of GdCl(3) significantly reduced the Caspase-3 activity and bile duct cell apoptosis at 2, 6, 12 and 24 h. After operation for 2, 6 and 12 h, the expression of Fas protein was lower in the GdCl(3) group than in the control group (P<0.05).


CONCLUSIONS
GdCl(3) plays an important role in suppressing bile duct cell apoptosis, including decreasing ALT, ALP, TBIL and TNF-α; suppressing Fas-FasL-Caspase signal transduction during transplantation.
Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Biao
B
Wang
Qi
Q
Zhang
Bili
B
Zhu
Zhonglin
Z
Cui
Jie
J
Zhou
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D001652:Bile Ducts / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D016031:Liver Transplantation; D008297:Male; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D012995:Solubility; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D052096:Warm Ischemia; D019014:fas Receptor / Q000097:blood
C491898:Fas protein, rat; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D005682:Gadolinium; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; C038958:gadolinium chloride