Liver Peroxisome Damage during Acute Hepatic Failure in Partial Ornithine Transcarbamylase Deficiency

Landrieu, P.; François, B.; Lyon, G; Vanhoof, F.

doi:10.1203/00006450-198212000-00001

Cited by 13 publications

(2 citation statements)

References 10 publications

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“…Specific autophagy of peroxisomes might have occurred. This explanation has been evoked in two conditions, in a patient with a major liver metabolic imbalance (Landrieu et al, 1982) and in the course of a continuous clofibrate treatment in mice (Vamecq & Van Hoof, 1984). In our experiments, only one animal out of seven displayed an apparent excess of peroxisomes in autophagic vacuoles.…”

Section: Ultrastructural Changesmentioning

confidence: 99%

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study

Hoof¹,

Hue²,

Vamecq³

et al. 1985

Biochemical Journal

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An ultrastructural and biochemical study of the toxic and hypoglycaemic effects of hypoglycin and pent-4-enoate was made on the livers of normal and clofibrate-fed rats. Injection of hypoglycin to rats doubles (from 22% to 44%) the volume fraction of mitochondria and decreases (from 1.05% to 0.26%) the volume fraction of peroxisomes in hepatocytes. The fast-acting toxin pent-4-enoate causes few ultrastructural changes except for the accumulation of lipids. In male adult rats fed with 0.5% clofibrate in their diet for 1-2 months, the volume fraction occupied by peroxisomes and mitochondria in hepatocytes rose to 6.26% and 29.5% respectively. Clofibrate feeding apparently protected the animals against the toxic, hypoglycaemic and hypothermic effects of hypoglycin and of pent-4-enoate, and completely prevented the ultrastructural damage caused by hypoglycin. After hypoglycin administration, hepatic mitochondrial butyryl-CoA dehydrogenase activity was inhibited by more than 90% and, surprisingly, the activity of the peroxisomal enzymes studied was largely preserved. When hypoglycin was given to rats fed on a clofibrate-containing diet, the oxidation of decanoylcarnitine, which was incomplete after hypoglycin treatment alone, remained incomplete with uncoupled mitochondria, but became apparently complete with coupled mitochondria. In the latter condition, there was a slowing of the rate during the last quarter of the pulse of oxygen uptake. Further, butyryl-CoA dehydrogenase activity was much less affected by hypoglycin in clofibrate-fed animals. Pent-4-enoate does not inhibit beta-oxidation in coupled mitochondria from clofibrate-treated rats.

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Section: Ultrastructural Changesmentioning

confidence: 99%

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study

Hoof¹,

Hue²,

Vamecq³

et al. 1985

Biochemical Journal

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“…Victims of this congenital disease usually do not survive past six months of age. Increased peroxisomal degradation has been implicated in acute hepatic failure in partial ornithine transcarbamylase deficiency also (90). An increased number of hepatic peroxisomes have been reported in several other pathological states such as alcoholic liver disease, certain infectious diseases, toxicosis, and Reye's syndrome (5,8,10,49).…”

Section: Peroxisomes In Diseasementioning

confidence: 99%

Effects of clofibric acid on porcine hepatocytes: a new model for the study of peroxisomal metabolism

Turteltaub

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Focal glycogenosis of the liver in disorders of ureagenesis: Its occurrence and diagnostic significance

Badizadegan

Perez‐Atayde

1997

Hepatology

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action of the urea cycle catalyzed by CPS, ammonia combines Metabolic disorders of ureagenesis can cause a Reye-like with adenosine triphosphate and bicarbonate to form carbasyndrome with potentially fatal hyperammonemia in children. myl phosphate. Carbamyl phosphate then reacts with orni-A mechanistically heterogeneous subset of these disorders thine to form citrulline in the first step of the actual urea shares the biochemical end-result of impaired mitochondrial synthesis in a reaction catalyzed by OTC. A deficiency in citrulline production. These include deficiencies of the mitoeither of these two enzymes will directly reduce mitochonchondrial enzymes, ornithine transcarbamylase (OTC) and drial citrulline production, and lead to impaired urea synthecarbamyl-phosphate synthase (CPS), as well as dibasic aminosis (Fig. 1). In contrast, impaired urea synthesis in dibasic acidurias hyperammonemia-hyperornithinemia-homocitrulaminoacidurias is the result of a functional deficiency in linuria (HHH) and lysinuric protein intolerance (LPI). In this citrulline production because of reduced mitochondrial ornireport, we present histopathology of the liver in 10 children thine levels. In hyperammonemia-hyperornithinemia-homowith defects of ureagenesis, including 6 with OTC deficiency, citrullinuria (HHH), the presumed defect is in the transport 3 with CPS deficiency, and 1 with HHH. The liver showed of cytoplasmic ornithine across the mitochondrial memdiffuse microvesicular steatosis, marked periportal nuclear branes ( Fig. 1). In lysinuric protein intolerance (LPI), the glycogen, and variable portal fibrosis with occasional delicate presumed defect is in the intestinal, hepatic, and renal transportal-to-portal bridging. Discrete aggregates of distended heport of ornithine and other dibasic amino acids. The defective patocytes with central nuclei and nonvacuolated clear cytointestinal absorption and reduced renal tubular reabsorption plasm were present in 5 of the 10 children, including two 2 of ornithine are thought to result in decreased plasma orni-OTC deficiency, 2 with CPS deficiency, and 1 with HHH.thine levels, which, in combination, with reduced hepatic Similar aggregates had been previously noted in the liver of some children with OTC deficiency or LPI, but their nature uptake, leads to reduced hepatocellular ornithine (Fig. 1). and diagnostic significance had so far remained unknown. Impaired citrulline production by any of the above mechaUsing special stains on frozen tissue sections and electron nisms can interfere with the catabolism of ammonia, causing microscopy, we show that the hepatocytes in these aggregates a Reye-like clinical syndrome with liver dysfunction and sehave little or no cytoplasmic neutral fat, but contain excessive vere, potentially fatal hyperammonemia in infancy or childfree cytoplasmic glycogen, morphologically mimicking a gly-hood. 1 cogen storage disease. In our experience, hepatocellular aggreHistopathology of the liver in CPS and OTC deficiencies gates of this nature do not occur in...

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Liver Peroxisome Damage during Acute Hepatic Failure in Partial Ornithine Transcarbamylase Deficiency

Cited by 13 publications

References 10 publications

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study

Effects of clofibric acid on porcine hepatocytes: a new model for the study of peroxisomal metabolism

Focal glycogenosis of the liver in disorders of ureagenesis: Its occurrence and diagnostic significance

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