Prostaglandin E1 improves survival rate after 95% hepatectomy in rats.
OBJECTIVE
Prostaglandin E1 (PGE1) has a wide-ranging effect on cytoprotection. Overproduction of heat shock protein 70 (HSP70) in the liver protects hepatocytes under various pathologic conditions. In this study, we examined the effect of a nontoxic HSP-inducer, PGE1, on acute liver failure after 95% hepatectomy in rats.


METHODS
PGE1 or vehicle was intravenously administered to rats 30 min before and during hepatectomy.


RESULTS
Nine of 30 rats pretreated with PGE1 survived, whereas all 20 rats pretreated with vehicle died within 96 h after operation. During the 24-h postoperative period, PGE1 significantly suppressed the release of alanine aminotransferase and elevation of hyaluronic acid. Histological examination showed that the vacuolized hepatocytes and round hepatocytes with pyknotic nuclei are frequently seen in rats pretreated with vehicle, whereas active regeneration is seen in rats pretreated with PGE1. During the first 24 h after surgery, HSP70 induction was absent in the residual livers of vehicle-treated rats. In contrast, PGE1 stimulated the HSP accumulation within 24 h, and viable hepatocytes contained abundant HSP70 in their nuclei.


CONCLUSIONS
Our results suggest that PGE1 may prevent acute liver failure after massive hepatectomy, at least in part, by enhancing HSP70 production in the residual liver.
Togo
Shinji
S
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. togo@med.yokohama-cu.ac.jp
Chen
Haochuan
H
Takahashi
Takuji
T
Kubota
Toru
T
Matsuo
Kenichi
K
Morioka
Daisuke
D
Watanabe
Kazuteru
K
Yamamoto
Harumi
H
Nagashima
Yoji
Y
Shimada
Hiroshi
H
D000410:Alanine Transaminase / Q000097:blood; D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006820:Hyaluronic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D017114:Liver Failure, Acute / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014665:Vasodilator Agents / Q000627:therapeutic use*
D018840:HSP70 Heat-Shock Proteins; D014665:Vasodilator Agents; D006820:Hyaluronic Acid; D000410:Alanine Transaminase; D000527:Alprostadil