Loss of microsomal components in drug-induced liver damage, in cholestasis and after administration of chemicals which stimulate heme catabolism

Matteis, Federico De

doi:10.1016/0362-5478(78)90011-6

Cited by 11 publications

(6 citation statements)

References 168 publications

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“…It was previously documented that a variety of chemicals including AAP could decrease the microsomal enzyme activity and heme contents of the liver. 40 Cytochrome P-450 has been considered to be a major microsomal enzyme that can provide heme molecules to be degraded oxidatively. 18 The mechanisms of CO production during the xenobiotic metabolism have long been investigated but are not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Carbon monoxide?mediated alterations in paracellular permeability and vesicular transport in acetaminophen-treated perfused rat liver

et al. 1999

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This study aimed to examine whether acetaminophen (AAP), an anti-inflammatory agent producing hepatocellular damages with its overdose, evokes hepatocellular dysfunction through mechanisms involving carbon monoxide (CO) generated by heme oxygenase (HO). In perfused rat livers, CO and bilirubin were determined in venous perfusate and bile samples as indices of heme degradation. Biliary excretion of transportally injected horseradish peroxidase was also determined to assess paracellular junctional permeability and vesicular transport across hepatocytes. AAP at 20 mmol/L induced a transient choleresis, followed by a reduction of bile output. Under these circumstances, the release of CO and bilirubin IXalpha, terminal products of the HO-mediated heme degradation, became 2. 5-fold greater than the control. The rate of CO production appeared stoichiometric to the degradation rate of microsomal cytochrome P-450. Mechanisms for the AAP-induced cholestasis involved an increase in the junctional permeability that coincided with a reduction of vesicular transport across hepatocytes. Clotrimazole, a cytochrome P-450 inhibitor, or zinc protoporphyrin IX, an HO inhibitor, but not copper protoporphyrin IX, which did not inhibit HO, attenuated these AAP-induced changes. Furthermore, administration of CO at concentrations comparable with those induced by AAP elicited a marked elevation of the paracellular junctional permeability concurrent with a reduction of transcellular vesicular transport, mimicking effects of the AAP administration. Thus, CO serves as a putative regulator of hepatocellular function that is overproduced through acute heme degradation during xenobiotic transformation.

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Section: Discussionmentioning

confidence: 99%

Carbon monoxide?mediated alterations in paracellular permeability and vesicular transport in acetaminophen-treated perfused rat liver

et al. 1999

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“…Accordingly, a greater loss of radioactivity from 14 C-ALA-prelabeled liver heme within the subsequent 24 h was found in fed mice compared to fed rats and in starved rats compared to fed rats (De Matteis, 1982). Such losses of radioactivity from 14 C-ALA-prelabeled liver homogenates could be further enhanced by treatment with Fe-dextran or CoCl 2 , two powerful HO-1 inducers, along with a significant loss of P450 content (De Matteis, 1982). In these experiments, the losses of 14 C-ALA-prelabeled liver radioactivity could all be correlated with the increased activity of liver ALAS1 at the end of the 24 h (Fig.…”

Section: Influence Of Heme Synthesis and Degradation On Hepatic P4mentioning

confidence: 99%

“…The liver ALAS1 values obtained at the end of the 24 h period are given as activity per total liver of 100 g body weight. The radioactivity lost from the total liver homogenate during the 24 h before killing was also calculated on a whole liver basis and is expressed as a percentage of the “zero time” radioactivity (De Matteis, 1982). The following statistical differences between groups applied to both radioactivity loss and ALAS activity: P < 0.02, when comparing values from fed and starved rats; P < 0.01, when comparing fed rats and fed mice; P < 0.001, when comparing treatment of rats with Fe-dextran and with dextran alone.…”

Section: Figuresmentioning

confidence: 99%

Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal

Correia

Sinclair²,

Matteis

2010

Drug Metabolism Reviews

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Heme is vital to our aerobic universe. Heme cellular content is finely tuned through an exquisite control of synthesis and degradation. Heme deficiency is deleterious to cells, whereas excess heme is toxic. Most of the cellular heme serves as the prosthetic moiety of functionally diverse hemoproteins, including cytochromes P450 (P450s). In the liver, P450s are its major consumers with >50% of hepatic heme committed to their synthesis. Prosthetic heme is the sine qua non of P450 catalytic biotransformation of both endo-and xenobiotics. This well-recognized functional role notwithstanding, heme also regulates P450 protein synthesis, assembly, repair and disposal. These less well-appreciated aspects are reviewed herein.

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“…Serum levels of griseofulvin are decreased by coadministration of phenobarbital. It has been reported that administration of this antibiotic markedly stimulates the activity of 5‐aminolevulinate synthase, the rate‐limiting enzyme of porphyrin synthesis, and causes a rapid inhibition of mitochondrial porphyrin‐metal chelatase and may thereby inhibit the synthesis of haem in the liver (De Matteis, 1982). Embryotoxic and teratogenic effects of griseofulvin have been demonstrated in pregnant rats exposed during organogenesis (De Carli & Larizza, 1988).…”

Section: Drug Interactions/adverse Reactionsmentioning

confidence: 99%

Antifungal agents of use in animal health – chemical, biochemical and pharmacological aspects

Bossche

Engelen

Rochette

2003

Vet Pharm & Therapeutics

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Loss of microsomal components in drug-induced liver damage, in cholestasis and after administration of chemicals which stimulate heme catabolism

Cited by 11 publications

References 168 publications

Carbon monoxide?mediated alterations in paracellular permeability and vesicular transport in acetaminophen-treated perfused rat liver

Carbon monoxide?mediated alterations in paracellular permeability and vesicular transport in acetaminophen-treated perfused rat liver

Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal

Antifungal agents of use in animal health – chemical, biochemical and pharmacological aspects

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