Inchinkoto, an herbal medicine, exerts beneficial effects in the rat liver under stress with hepatic ischemia-reperfusion and subsequent hepatectomy.
OBJECTIVE
To investigate the beneficial effects of inchinkoto (ICKT) in the liver after 70% hepatectomy following ischemia reperfusion.


METHODS
Wistar rats were divided into 3 groups: simple laparotomy and 70% hepatectomy (Hx), 70% hepatectomy following ischemia reperfusion (IR) with vehicle (IRHxV), 70% hepatectomy following IR with ICKT (1 or 2 g/kg of body weight; IRHxK). Vehicle or ICKT was administered for 3 days preoperatively. The hepatoduodenal ligament was clamped for 15 minutes before hepatectomy in the IRHx groups. Rats were killed 1 hours after hepatectomy. In other experiments, the hepatoduodenal ligament was clamped for 30 minutes, with or without ICKT treatment, to evaluate the effect of ICKT on IR injury-induced mortality. Serum transaminase levels and the gene expression of inflammatory cytokines and inducible nitric oxide synthase in the remnant liver were determined. Furthermore, the expression of antioxidant genes was evaluated by PCR array.


RESULTS
The elevation of serum transaminase levels, the upregulation of genes for inflammatory cytokines and inducible nitric oxide synthase, and the increased formation of nitrotyrosine observed in the remnant livers of the IRHxV group were all significantly attenuated by preoperative administration of ICKT in the IRHxK group. The expression of antioxidant genes was also higher in the IRHxK group compared with that of the IRHxV group. Moreover, administration of ICKT significantly reduced the mortality induced by IRHx after 30-minute ischemia.


CONCLUSIONS
Preoperative administration of ICKT provides beneficial effects through attenuating inflammatory responses and oxidative stress in the liver following IR and subsequent hepatectomy.
Kawai
Kiyotaka
K
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Yokoyama
Yukihiro
Y
Kokuryo
Toshio
T
Watanabe
Katsutaka
K
Kitagawa
Tomomi
T
Nagino
Masato
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006498:Hepatectomy; D018836:Inflammation Mediators / Q000378:metabolism; D057889:Iridoid Glycosides; D039823:Iridoids / Q000494:pharmacology; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate; D000637:Transaminases / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D057889:Iridoid Glycosides; D039823:Iridoids; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C078038:inchinko-to; C002744:3-nitrotyrosine; D014443:Tyrosine; C007834:genipin; D019001:Nitric Oxide Synthase; D000637:Transaminases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione