Preventive effects of the deleted form of hepatocyte growth factor against various liver injuries

被引：31

作者：

Masunaga, H ^{[1
]}

Fujise, N ^{[1
]}

Shiota, A ^{[1
]}

Ogawa, H ^{[1
]}

Sato, Y ^{[1
]}

Imai, E ^{[1
]}

Yasuda, H ^{[1
]}

Higashio, K ^{[1
]}

机构：

[1] Snow Brand Milk Prod Co Ltd, Life Sci Res Inst, Ishibashi, Tochigi 32905, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1998年 / 342卷 / 2-3期

关键词：

HGF (hepatocyte growth factor); hepatic disorder; coagulopathy; hepaplastin test; endotoxin;

D O I：

10.1016/S0014-2999(97)01485-4

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The effects of a naturally occurring deleted form of hepatocyte growth factor (HGF) on hepatic disorder were studied in various models of hepatic failure. The pretreatment of rats and mice with the deleted form of HGF prevented the liver injuries and coagulopathy induced by endotoxin, dimethylnitrosamine and acetaminophen and reduced the mortality due to hepatic dysfunction induced by these hepatotoxins. The concurrent administration of the deleted form of HGF also prevented the liver injury and hepatic fibrosis in mice treated with alpha-naphthylisothiocyanate and in rats treated with dimethylnitrosamine. Moreover, the deleted form of HGF normalized the results of the bromosulphalein-clearance test and ameliorated jaundice in rats with periportal cholangiolitic hepatopathy induced by alpha-naphthylisothiocyanate. The deleted form of HGF also reversed the coagulopathy in rats with hepatic disorder induced by dimethylnitrosamine or by 70% resection of cirrhotic liver (induced by carbon tetrachloride). In Long-Evans cinnamon rats receiving vehicle, 20 out of 21 animals died within 4 days after the onset of jaundice. jaundice. After infusion of the deleted form of HGF for 4 days, 7 out of 20 Long-Evans cinnamon rats survived. These results indicate that the deleted form of HGF could have therapeutic potency in patients with severe hepatic failure. (C) 1998 Elsevier Science B.V.

引用

页码：267 / 279

页数：13

共 38 条

[1] OXYGEN-DERIVED FREE-RADICALS PROMOTE HEPATIC-INJURY IN THE RAT [J].

ARTHUR, MJP ;

BENTLEY, IS ;

TANNER, AR ;

SAUNDERS, PK ;

MILLWARDSADLER, GH ;

WRIGHT, R .

GASTROENTEROLOGY, 1985, 89 (05) :1114-1122

[2]

ATILLASOY E, 1995, ANNU REV MED, V46, P181

[3]

BARAONA E, 1993, LIFE SCI, V52, P1249

[4] SUPEROXIDE DISMUTASE - IMPROVED ASSAYS AND AN ASSAY APPLICABLE TO ACRYLAMIDE GELS [J].

BEAUCHAM.C ;

FRIDOVIC.I .

ANALYTICAL BIOCHEMISTRY, 1971, 44 (01) :276-&

[5] PREVENTION OF PARACETAMOL-INDUCED LIVER-DAMAGE IN MICE WITH GLUTATHIONE [J].

BENEDETTI, MS ;

LOUIS, A ;

MALNOE, A ;

SCHNEIDER, M ;

LAM, R ;

KREBER, L ;

SMITH, RL .

JOURNAL OF PHARMACY AND PHARMACOLOGY, 1975, 27 (08) :629-632

[6] HEMOSTASIS AND FIBRINOLYSIS IN SEVERE LIVER-FAILURE AND THEIR RELATION TO HEMORRHAGE [J].

BOKS, AL ;

BROMMER, EJP ;

SCHALM, SW ;

VANVLIET, HHDM .

HEPATOLOGY, 1986, 6 (01) :79-86

[7] A SEVERE COMBINED IMMUNODEFICIENCY MUTATION IN THE MOUSE [J].

BOSMA, GC ;

CUSTER, RP ;

BOSMA, MJ .

NATURE, 1983, 301 (5900) :527-530

[8] ACUTE LIVER-FAILURE [J].

CARACENI, P ;

VANTHIEL, DH .

LANCET, 1995, 345 (8943) :163-169

[9] REDUCED GLUTATHIONE INHIBITS THE ALKYLATION BY N-NITROSODIMETHYLAMINE OF LIVER DNA INVIVO AND MICROSOMAL FRACTION INVITRO [J].

FREI, E ;

BERTRAM, B ;

WIESSLER, M .

CHEMICO-BIOLOGICAL INTERACTIONS, 1985, 55 (1-2) :123-137

[10] GLUCAGON AND INSULIN FOR THE TREATMENT OF HEPATIC-FAILURE IN DIMETHYLNITROSAMINE-INTOXICATED RATS [J].

FUJIWARA, K ;

OGATA, I ;

MISHIRO, S ;

OHTA, Y ;

OKA, Y ;

TAKATSUKI, K ;

SATO, Y ;

HAYASHI, S ;

YAMADA, S ;

OKA, H .

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1988, 23 (05) :567-573

← 1 2 3 4 →