Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats.
OBJECTIVE
To investigate the possibility in rats that ONO-5046 Na, a new recombinant inhibitor of neutrophil elastase, can reduce hepatic metastases induced by ischaemia-reperfusion.


METHODS
Laboratory experimental study.


METHODS
Research laboratory, Japan.


METHODS
Male Fischer rats.


METHODS
Rats underwent 60 min of 70% partial hepatic ischaemia, after which rat colon adenocarcinoma cells (RCN-H4) were injected into the spleen. The animals were divided into two test groups and a control group. One group was given ONO-5046 Na intravenously at 10 mg/kg/hour. A second group was given a saline solution for the same period, while the controls were not made ischaemic.


METHODS
Three weeks after inoculation, the number of tumour nodules on the liver surface was counted. The anti-cancer effect of ONO-5046 Na was measured by monotetrazolium assay.


RESULTS
Hepatic ischaemia-reperfusion increased the number of liver metastases of RCN-H4 in both clamped and unclamped hepatic lobes. ONO-5046 Na significantly inhibited this in unclamped lobes, but had no anti-cancer effect.


CONCLUSIONS
Neutrophil elastase may have an important role in increasing haematogenous liver metastases by ischaemia-reperfusion, particularly in unclamped lobes.
Doi
Koji
K
Second Department of Surgery, Fukui Medical University, Yoshida-gun, Fukui, Japan.
Horiuchi
Tetsuya
T
Uchinami
Masaru
M
Tabo
Takanori
T
Kimura
Narisato
N
Yokomachi
Jun
J
Yoshida
Makoto
M
Tanaka
Kuniyoshi
K
D000818:Animals; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008102:Liver Circulation / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000150:complications*; D015843:Serpins / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D015843:Serpins; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine