Abstract

The response of the liver to a single oral or intraperitoneal dose of the hypolipidemic drug nafenopin has been investigated in rats. Liver weight increased for 3 days and returned to normal in 6 days, although at no time did food consumption differ from that of controls. During the experimental period, liver protein concentrations were unchanged while DNA concentration decreased slightly. Ornithine decarboxylase activity, DNA synthesis and amino acid uptake were markedly stimulated, as has been reported in the regenerating liver. After intraperitoneal nafenopin the onset of these responses was more rapid and the degree of induction greater than that seen after oral nafenopin. Since ornithine decarboxylase and DNA synthesis increased at approximately the same time after orally administered nafenopin, there is some doubt as to whether induction of ornithine decarboxylase is obligatory prior to the synthesis of DNA. The results,however, do support a role for increased amino acid uptake in the pre-replicative phase of liver growth. It is speculated that the oral/intraperitoneal difference in induction rates of these parameters may be attributable to a slow rate of disposition of orally administered nafenopin in the rat or to an unknown alternative mechanism.

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