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Biochemical effects of 3,5-diethoxycarbonyl-1, 4-dihydrocollidine in mouse liver

Gayathri, A Keshavamurthy and Padmanaban, Govindarajan (1974) Biochemical effects of 3,5-diethoxycarbonyl-1, 4-dihydrocollidine in mouse liver. In: Biochemical Pharmacology, 23 (19). pp. 2713-2725.

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3,5-Diethoxycarbonyl-1,4-dihydrocollidine (DDC) is a porphyrinogenic agent and is a powerful inducer of δ-aminolaevulinate synthetase, the first and rate-limiting enzyme of the haem-biosynthetic pathway, in mouse liver. However, DDC strikingly inhibits mitochondrial as well as microsomal haem synthesis by depressing the activity of ferrochelatase in vivo. The drug on repeated administration to female mice has been found to elicit hypertrophic effects in the liver microsomes initially, but the effects observed at later stages denote either hyperplasia or increase in polyploidal cells. The microsomal protein concentration shows a striking decrease with repeated doses of the drug. The rate of microsomal protein synthesis in vivo as well as in vitro shows an increase with two injections of DDC but decreases considerably with repeated administration of the drug. The activities of NADPH-cytochrome creductase and ribonuclease are not affected in the liver microsomes of drug-treated animals when expressed per mg of microsomal protein. DDC has also been found to cause degradation of microsomal haem, which is primarily responsible for the decrease in cytochrome P-450 content. The drug also leads to a decrease in mitochondrial cytochrome c levels due to inhibition of haem synthesis and also due to degradation of mitochondrial haem at later stages. The biochemical effects of the drug are compared and discussed with those reported for allylisopropylacetamide and phenobarbital.

Item Type: Journal Article
Publication: Biochemical Pharmacology
Publisher: Elsevier Science
Additional Information: Copyright of this article belongs to Elsevier Science.
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 10 Sep 2009 05:54
Last Modified: 19 Sep 2010 05:44
URI: http://eprints.iisc.ac.in/id/eprint/23129

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