TCV-116, an angiotensin II type 1 receptor antagonist, reduces hepatic ischemia-reperfusion injury in rats.
BACKGROUND
In Pringle's maneuver during liver surgery and liver transplantation, ischemia-reperfusion (I/R) is an unavoidable process, and protection against hepatic I/R injury is a major unresolved problem. Therefore, various pharmacologic approaches to prevent hepatic I/R injury are currently under trial. In this study, we investigated whether TCV-116, an angiotensin II type 1 receptor antagonist, can reduce this injury.


METHODS
The rats were pretreated either with TCV-116 (group 1) or with the vehicle alone (group 2). The rats in group 3 were not pretreated. Thereafter, they were subjected to partial hepatic I/R.


RESULTS
After reperfusion, the mean peak plasma concentrations of aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, and creatine kinase were lower in group 1 than in groups 2 and 3. The magnitude of hepatic injury was reduced in group 1 compared with that in groups 2 and 3. The mean peak plasma concentrations of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractants-1, and interleukin-6 were lower in group 1 than in groups 2 and 3. The number of neutrophils infiltrating the liver was also lower in group 1 than in groups 2 and 3. The mean peak plasma concentration of hepatocyte growth factor (HGF) was higher in group 1 than in groups 2 and 3.


CONCLUSIONS
TCV-116 reduced the hepatic I/R injury by inhibiting inflammatory cytokine production and by enhancing HGF production.
Araya
Jun
J
Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan 060-0061.
Tsuruma
Tetsuhiro
T
Hirata
Koichi
K
Yagihashi
Atsuhito
A
Watanabe
Naoki
N
D000410:Alanine Transaminase / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D016207:Cytokines / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D044140:Receptor, Angiotensin, Type 1; D015427:Reperfusion Injury / Q000517:prevention & control*; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016207:Cytokines; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase; C077793:candesartan cilexetil