Defense Date


Document Type


Degree Name

Doctor of Philosophy



First Advisor

W. L. Banks, Jr.


Ornithine plays an important role in mammalian intermediary metabolism. Ornithine can be (1) utilized as a component of the urea cycle, (2) decarboxylated to form putrescine, a precursor of the polyamines, spermidine and spermine, and (3) converted metabolically to arginine, proline and glutamate. In prior investigations conducted in our laboratories and others, free endogenous hepatic pools of ornithine were found to be elevated following hydrazine administration. Consequently, time-course alterations of arginase, ornithine δ-transaminase, ornithine transcarbamylase, and ornithine decarboxylase activities were investigated regarding the effect of hydrazine treatment on hepatic ornithine metabolism in the rat. As an outgrowth of these investigations, a time-course study of the hepatic concentration of putrescine, spermidine and spermine was warranted.

Male albino rats (Holtzman) were injected with neutralized hydrazine (40 mg/kg, body weight, ip) or isotonic saline (1.0 ml/kg, body weight, ip) and fasted for various times. The effects ascribed to hydrazine treatment were based on the comparison of results from hydrazine-treated animals with those obtained from the saline-injected control animals. Maximal elevations of endogenous hepatic ornithine pool sizes were observed at 12 hr in supernatant preparations (1000% of control) and at 24 hr in homogenate preparations (600% of control). Hepatic arginase activity was found to reach its nadir at 4 hr (70% of control). Thus, arginase did not appear to be responsible for the increased ornithine levels resulting from hydrazine treatment. Hepatic ornithine δ-transaminase activity was decreased (40% of control) at 4 hr and this level of activity was sustained throughout the 24 hr period examined. Hepatic ornithine transcarbamylase activity was shown to be decreased maximally at 12 hr (40% of control). The decreased activities of these latter two enzymes offers a plausible explanation for the increased hepatic ornithine levels following hydrazine treatment. Although a remarkable increase (1500% of control) in ornithine decarboxylase activity was observed at 4 hr, it was not thought to influence significantly the levels of hepatic ornithine since the relative activities of the other enzymes involved in ornithine metabolism have been shown by others to be considerably greater than ornithine decarboxylase. This increase in ornithine decarboxylase activity was followed by sequential elevations in total endogenous hepatic putrescine and then spermidine levels. The total endogenous hepatic spermine levels were not altered except for a slight decrease at 48 hr.

Regenerating liver following partial hepatectomy demonstrated alterations similar in magnitude, but with a different time-course in the changes in these parameters. These similarities along with other biochemical and morphological alterations established by others following either partial hepatectomy or hydrazine treatment suggest that the latter may be tantamount to a "chemical" partial hepatectomy.


Scanned, with permission from the author, from the original print version, which resides in University Archives.


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