The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine

C. W. Putnam, A. R. Buckley, James A Warneke, F. M. Karrer, B. Rhenman, K. Steinbronn

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Hepatic neutral serine proteases (including plasminogen activator) and ornithine decarboxylase (ODC) are induced by the hepatotoxin galactosamine (GALN). We examined the hepatoprotection conferred by ε-aminocaproic acid (EACA), a fibrinolytic inhibitor, putrescine (PUTR), the polyamine generated from ornithine by ODC, and α-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. GALN, 450 mg/kg, was administered intraperitoneally to Wistar-Lewis rats (group I). Groups II, III, and IV were also given EACA (80 mg/kg), PUTR (0.3 mmol/kg), or DFMO (0.3 mmol/kg), respectively, 1 hour before and 3, 7, and 12 hours after GALN. Rats were killed 2 hours after an intraperitoneal dose of 3H-thymidine was administered, 30 or 45 hours after GALN. EACA and PUTR were effective protectants against necrosis as judged by enzymes and histologic findings. Neither increased thymidine incorporation above the levels seen with GALN only. DFMO offered no protection even though thymidine incorporation at 45 hours was increased. Both EACA and PUTR, which have similar chemical structures, possessed significant antiprotease activity in vitro, suggesting that they act by inhibiting toxin-induced neutral serine protease activity and not by accelerating regeneration.

Original languageEnglish (US)
Pages (from-to)214-222
Number of pages9
JournalSurgery
Volume96
Issue number2
StatePublished - 1984
Externally publishedYes

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Aminocaproic Acid
Galactosamine
Putrescine
Eflornithine
Thymidine
Ornithine Decarboxylase
Serine Proteases
Ornithine
Plasminogen Activators
Polyamines
Protease Inhibitors
Wistar Rats
Regeneration
Necrosis
Liver
Enzymes

ASJC Scopus subject areas

  • Surgery

Cite this

Putnam, C. W., Buckley, A. R., Warneke, J. A., Karrer, F. M., Rhenman, B., & Steinbronn, K. (1984). The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine. Surgery, 96(2), 214-222.

The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine. / Putnam, C. W.; Buckley, A. R.; Warneke, James A; Karrer, F. M.; Rhenman, B.; Steinbronn, K.

In: Surgery, Vol. 96, No. 2, 1984, p. 214-222.

Research output: Contribution to journalArticle

Putnam, CW, Buckley, AR, Warneke, JA, Karrer, FM, Rhenman, B & Steinbronn, K 1984, 'The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine', Surgery, vol. 96, no. 2, pp. 214-222.
Putnam CW, Buckley AR, Warneke JA, Karrer FM, Rhenman B, Steinbronn K. The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine. Surgery. 1984;96(2):214-222.
Putnam, C. W. ; Buckley, A. R. ; Warneke, James A ; Karrer, F. M. ; Rhenman, B. ; Steinbronn, K. / The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine. In: Surgery. 1984 ; Vol. 96, No. 2. pp. 214-222.
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