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The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D‐galactosamine

Francavilla, A and Dileo, A and Polimeno, L and Gavaler, J and Pellicci, R and Todo, S and Kam, I and Prelich, J and Makowka, L and Starzl, TE (1986) The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D‐galactosamine. Hepatology, 6 (6). 1346 - 1351. ISSN 0270-9139

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Abstract

Galactosamine induces a dose‐dependent hepatic injury in rats and many other animals. The toxicity of D‐galactosamine appears to be a consequence of the loss of hepatic UTP. It has previously been reported that regenerating liver cytosol is able to prevent, at least in part, the lethal effect of this substance by stimulating hepatic regeneration. Recently, we have separated a fraction using alcohol precipitation (80%) from regenerating liver cytosol and from weanling rat liver cytosol prepared in acetate buffer (100 mM, pH 6.5). We named this fraction hepatic stimulatory substance because of its ability to stimulate DNA synthesis in vivo when injected intraperitoneally in 40% hepatectomized rats and in vitro in the presence of hepatocytes isolated and maintained in monolayer cultures. The stimulatory activity of the hepatic stimulatory substance is fully evident in subfractions of molecular weight up to 300,000 and 50,000 daltons of the crude material obtained using Amicon Ultra membrane filters. The present report describes the ability of hepatic stimulatory substance and its subfractions to stimulate hepatocyte proliferation and the application of these hepatic extracts in successfully reversing the lethality of D‐galactosamine‐induced hepatic necrosis in rats. D‐Galactosamine (2.6 gm per kg of body weight) was administered intraperitoneally to 438 male Lewis strain rats. The animals were divided into six groups according to the type of treatment: Group 1 (n = 131) saline; Group 2 (n = 40) cytosol (75 mg total protein); Group 3 (n = 75) hepatic stimulatory substance (20 mg total protein); Group 4 (n = 42) 300,000 subfraction (4 mg total protein); Group 5 (n = 68) 300,000 subfraction (2 mg total protein), and Group 6 (n = 82) 50,000 subfraction (0.6 mg total protein). All rats received 4 ml of the test solution intraperitoneally at 48 hr after D‐galactosamine administration. The percentage of rats surviving in each group was determined daily for 20 days. Although hepatic stimulatory substance and 50,000 subfraction tended to improve survival in intoxicated rats, only those rats treated with the 300,000 subfraction attained statistical significance with respect to the saline control. Copyright © 1986 American Association for the Study of Liver Diseases


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Francavilla, A
Dileo, A
Polimeno, L
Gavaler, J
Pellicci, R
Todo, S
Kam, I
Prelich, J
Makowka, L
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1986
Date Type: Publication
Journal or Publication Title: Hepatology
Volume: 6
Number: 6
Page Range: 1346 - 1351
DOI or Unique Handle: 10.1002/hep.1840060621
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0270-9139
Other ID: uls-drl:31735062116359, Starzl CV No. 673
Date Deposited: 08 Apr 2010 17:11
Last Modified: 16 Oct 2017 05:55
URI: http://d-scholarship.pitt.edu/id/eprint/4059

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