Alterations of Hepatic Endoplasmic Reticulum in Porphyric Rats

Posalaki, Zoltan; Barka, Tibor

doi:10.1177/16.5.337

Cited by 15 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The induction of ALAS by AIA in the rat is accompanied by an array of morphological alterations that are demonstratable by electron microscopy. These include: (a) hypertrophy of hepatocytes, (b) volume enlargements of cytoplasm, nucleus, and nucleoli of hepatocytes, (c) accumulation of lipoproteinlike granules within the cisternae of the SER, (d) formation of lipid droplets in the cytoplasm, and (e) proliferation of the SER (9)(10)(11). The mitochondria, however, show surprisingly little morphological change depsite the fact that the newly synthesized ALAS localizes in these structures.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Postnatal Development on Drug-Induced Hepatic Porphyria and the Synthesis of Cytochrome P-450

Cao

Moses

Rosenthal

et al. 1971

The Journal of Experimental Medicine

View full text Add to dashboard Cite

The mitochondrial enzyme δ-aminolevulinate synthetase (ALAS) controls the rate-limiting step in the synthesis of porphyrins and heme. An experimental form of hepatic porphyria can be readily elicited in laboratory animals, such as the rat, by drugs and foreign chemicals which are known to enhance the de novo formation of this enzyme in the liver. The present study shows that there is a striking refractoriness to the induction of ALAS during the perinatal period in the rat. Chemicals which have potent porphyria-inducing activity in adult animals have no significant inducing effect on hepatic ALAS in neonates. The ultrastructural changes which accompany the induction of ALAS by drugs and chemicals in adult liver also fail to take place in the livers of neonates. A progressive capacity for responding to the action of chemical inducers of hepatic ALAS does, however, develop in neonatal animals so that by approximately 5–6 wk of age experimental porphyria can be elicited as effectively in them as in adults. The reasons for the refractoriness of hepatic ALAS to induction in the perinatal period are not known; but the findings of this study make it clear that ALAS belongs to that increasingly large group of liver enzymes in mammals whose appearance, increase of activity, or inducibility is developmentally determined. The occurrence of developmental changes in the indicibility of ALAS in the liver of neonates also provided an opportunity to study the relationship of this enzyme activity to the drug-mediated induction of the hepatic hemoprotein cytochrome P-450. This inducible hemoprotein serves as the terminal oxygenase in the microsomal mixed-function oxidase system in the liver. The results of this study indicate that, in contrast to the refractoriness of ALAS to induction, significant drug-induced changes of hepatic P-450 content and of hemeprecursor incorporation into this cytochrome do take place in neonates. The synthesis of P-450 thus appears to be under a regulatory control different from that of ALAS in neonates, and the relation between ALAS activity and P-450 formation is not therefore a direct one.

show abstract

Section: Discussionmentioning

confidence: 99%

The Influence of Postnatal Development on Drug-Induced Hepatic Porphyria and the Synthesis of Cytochrome P-450

Cao

Moses

Rosenthal

et al. 1971

The Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…Although detailed studies are not available, administration of allylisopropylacetamide causes an increase in liver weight, total protein and lipid contents (Marver et al, 1966b;Lottsfeld & Labbe, 1965). Allylisopropylacetamide also causes proliferation of the smooth endoplasmic reticulum (Moses et al, 1970;Biempica etal., 1967;Posalaki & Barka, 1968).…”

mentioning

confidence: 99%

Biochemical effects of the porphyrinogenic drug allylisopropylacetamide. A comparative study with phenobarbital

Padmanaban

1973

Biochemical Journal

View full text Add to dashboard Cite

Successive administrations of allylisopropylacetamide, a potent porphyrinogenic drug, increase liver weight, microsomal protein and phospholipid contents. There is an increase in the rate of microsomal protein synthesis in vivo and in vitro. The drug decreases microsomal ribonuclease activity and increases NADPH-cytochrome c reductase activity. Phenobarbital, which has been reported to exhibit all these changes mentioned, is a weaker inducer of delta-aminolaevulinate synthetase and increases the rate of haem synthesis only after a considerable time-lag in fed female rats, when compared with the effects observed with allylisopropylacetamide. Again, phenobarbital does not share the property of allylisopropylacetamide in causing an initial decrease in cytochrome P-450 content. Haematin does not counteract most of the biochemical effects caused by allylisopropylacetamide, although it is quite effective in the case of phenobarbital. Haematin does not inhibit the uptake of [2-(14)C]allylisopropylacetamide by any of the liver subcellular fractions.

show abstract

The Effects of Progesterone Administration on Hepatic Endoplasmic Reticulum: An Electron Microscopic and Biochemical Study

Jones

Emans

1969

Metabolic Effects of Gonadal Hormones and Contraceptive Steroids

View full text Add to dashboard Cite

Alterations of Hepatic Endoplasmic Reticulum in Porphyric Rats

Cited by 15 publications

References 0 publications

The Influence of Postnatal Development on Drug-Induced Hepatic Porphyria and the Synthesis of Cytochrome P-450

The Influence of Postnatal Development on Drug-Induced Hepatic Porphyria and the Synthesis of Cytochrome P-450

Biochemical effects of the porphyrinogenic drug allylisopropylacetamide. A comparative study with phenobarbital

The Effects of Progesterone Administration on Hepatic Endoplasmic Reticulum: An Electron Microscopic and Biochemical Study

Contact Info

Product

Resources

About