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Biomedical subjects

D Pessayre

Publications and source records attributed to D Pessayre.

At least 181 records · Page 10Linked to original sources
PubMed1980

[Hepatitis due to ajmaline. Report of cases and review of the literature].

The authors report the cases of 4 patients with jaundice following the administration of ajmaline. The disease had a pseudo- angiocholitic onset with fever, chills and pruritus in the 4 patients and abdominal pains in 2 patients. Serum transaminase activity and serum alkaline phosphatase activity were increased in the 4 patients. Blood eosinophilia was found in 3 patients. Liver lesions included predominantly centrilobular cholestasis, mild hepatocytic lesions, and portal inflammation. After the interruption of the drug administration, recovery occurred in the 4 patients. Two patients resumed the intake of ajmaline; transient hepatitis recurred in these 2 patients.

Adult↗
PubMed1979

Gold salt-induced cholestasis.

The authors report the case of a patient with transient intrahepatic cholestasis following the administration of a soluble gold salt, sodium aurothiopropanol sulfonate. Other manifestations of intolerance to gold salts included exfoliative dermatitis and eosinophilia.

Aged↗
PubMed1979

Inhibition of hepatic drug-metabolizing enzymes by arachidonic acid.

1. The effects of arachidonic acid on hepatic drug-metabolizing enzymes was investigated in male ICR-Swiss mice. 2. A single administration of arachidonic acid, 100 mg/kg i.p., doubled the hexobarbital sleeping time. Arachidonic acid in vitro gave a type I binding spectrum with hepatic microsomes; it inhibited the metabolism of hexobarbital and of ethylmorphine, two type I binding drugs, but not that of aniline, a type II binding drug; the inhibition of hexobarbital metabolism by arachidonic acid was competitive. 3. Repeated administration of arachidonic acid up to a total dose of 1000 mg/kg i.p., either in the course of 5 hours, or in the course of 5 days, decreased microsomal cytochrome P-450 levels and NADPH-cytochrome c reductase activity. 4. It is concluded that the administration of arachidonic acid may impair drug metabolism in two ways, mainly, by competitively inhibiting the activity of drug-metabolizing enzymes, and secondarily, by decreasing the hepatic concentration of these enzymes.

Animals↗
PubMed1979

Effect of fasting on metabolite-mediated hepatotoxicity in the rat.

Acetaminophen and bromobenzene are transformed in the liver into chemically reactive metabolites that may either bind to glutathione and be detoxified or bind to hepatic proteins and produce liver cell necrosis. Fasting for 42 hr (a) decreased hepatic glutathione concentration, (b) increased the amount of chemically reactive metabolite irreversibly bound to hepatic proteins after administration of 3H-acetaminophen or 14C-bromobenzene, and (c) increased the hepatotoxicity of acetaminophen or bromobenzene. In rats fasted for various lengths of time, there was an inverse relationship between the concentration of glutathione in the liver and the activity of serum glutamic pyruvic transaminases after administration of acetaminophen or bromobenzene. In vitro, there was an inverse relationship between the concentration of glutathione in the incubate and the amount of chemically reactive metabolite bound to microsomal proteins after incubation of 3H-acetaminophen or 14C-bromobenzene with hepatic microsomes. It is concluded that fasting may decrease the inactivation of chemically reactive metabolites by glutathione, increase their binding to hepatic proteins, and enhance the hepatotoxicity of drugs transformed into chemically reactive metabolites that are detoxified by binding to glutathione.

Acetaminophen↗
PubMed1979

[Reactive metabolites of xenobiotics : their role in the hepatotoxicity of drugs].

Certain drugs are transformed into reactive metabolites by cytochrome P-450, a hepatic microsomal enzyme. The reactive metabolites covalently bind to hepatocyte macromolecules, thus determining liver lesions. Induction of microsomial enzymes increases the formation of reactive metabolites and exaggerates hepatotoxicity of these drugs.

Acetaminophen↗
PubMed1979

Perhexiline maleate-induced cirrhosis.

The authors report the cases of 2 patients who died from cirrhosis after receiving perhexiline maleate, a drug widely used in Europe for the treatment of angina pectoris. Perhexiline maleate had been ingested for 24 and 28 mo, respectively. Manifestations of cirrhosis included jaundice, hepatic encephalopathy, ascites, and portal hypertension. Associated manifestations of intolerance to perhexiline maleate included peripheral neuropathy in 1 patient and marked weight loss in both. Histologic lesions resembled those observed in patients with alcoholic liver disease. Ultrastructural lesions included numerous enlarged lysosomes containing myeloid figures. Histochemical stains demonstrated increased phospholipid content of the hepatocytes. These findings are consistent with the view that prolonged administration of perhexiline maleate may induce both histologic lesions resembling those of alcoholic liver disease and ultrastructural and histochemical lesions resembling those of phospholipidosis.

Aged↗
PubMed1978

Effect of surgery under general anaesthesia on antipyrine clearance.

1 The effect of surgery under general anaesthesia on drug metabolism was investigated in man. The activity of hepatic drug-metabolizing enzymes was evaluated by measurement of antipyrine clearance, before surgery and 3 days after surgery, in eighteen patients. 2 In those patients in whom the operation lasted 2 h or less, the postoperative clearance of antipyrine was significantly (P less than 0.05) increased by 48%; in those patients in whom the operation lasted 2--4 h, it was non-significantly decreased by 36%; in those patients in whom the operation lasted more than 4 h, it was significantly decreased by 47% (P less than 0.01). 3 It is concluded (a) that short operations are followed by increased activity of hepatic drug-metabolizing enzymes, whereas (b) protracted operations are followed by decreased activity. It is suggested (a) that the former effect may be a consequence of enzyme induction by drugs used for premedication and anaesthesia, whereas (b) the latter effect may be the result of major surgical trauma.

Adult↗
PubMed1978

Metabolic activation of trichloroethylene into a chemically reactive metabolite toxic to the liver.

The mechanism for trichloroethylene hepatotoxicity was investigated in male Sprague-Dawley rats. Phenobarbital pretreatment increased and CoCl2 pretreatment decreased trichloroethylene hepatotoxicity. After administration of 1(14)C]trichloroethylene, a radioactive material became irreversibly bound to hepatic proteins, while negligible amounts were bound to muscle proteins. When 1(14)C]trichloroethylene was incubated under air with hepatic microsomes and a NADPH-generating system, a radioactive material became irreversibly bound to microsomal proteins; binding was negligible when the NADPH-generating system was omitted; binding was inhibited by carbon monoxide and by piperonyl butoxide; the amount of bound material was greater with microsomes from phenobarbital-pretreated rats and lower with microsomes from CoCl2-pretreated rats than with microsomes from nonpretreated rats. Trichloroethylene administration decreased hepatic glutathione in normal rats but not in piperonyl butoxide-pretreated rats; in vitro, glutathione decreased the amount of trichloroethylene material that bound to microsomal proteins. The reported results are consistent with the view that 1) trichloroethylene is metabolized by cytochrome P-450 into a chemically reactive metabolite which reacts with, and binds to, either proteins or glutathione, 2) binding to proteins produces liver lesions and 3) binding to glutathione decreases the amount of reactive metabolite available for binding to proteins.

Animals↗
PubMed1978

Iproclozide fulminant hepatitis. Possible role of enzyme induction.

The authors report the cases of 3 patients who died from fulminant hepatitis after receiving iproclozide, a hydrazine-containing monoamine oxidase inhibitor. Fulminant hepatitis in these patients resembled that reported in patients receiving other hydrazine-containing monoamine oxidase inhibitors: (1) the 3 patients were women; (2) the monoamine oxidase inhibitor has been ingested for 1 month or more; (3) the main clinical manifestations were jaundice and disorders of consciousness; (4) hypersensitivity manifestations were absent; (5) the predominant liver lesion was necrosis; (6) all 3 patients died. In our 3 patients, jaundice occurred 7 to 10 days after the adjunction to iproclozide of a microsomal enzyme inducer. These observations suggest that concomitant administration of iproclozide and of microsomal enzyme inducers may produce fulminant hepatitis in man. It is speculated that iproclozide could be, like iproniazid, transformed into a hepatotoxic metabolite, the production of which would be increased by microsomal enzyme induction.

Adult↗
PubMed1977

[Effects of hepato-biliary diseases on drug metabolism (author's transl)].

Drug metabolism may be impaired in patients with hepato-biliary diseases. Hepatocellular failure may decrease the rate of drug biotransformation; cholestasis may decrease 1) the absorption of lipid soluble drugs, 2) the rate of drug biotransformation, and 3) the biliary excretion of drugs. Activity and/or toxicity are modified variously as either the drug or a metabolite of it is the active and/or toxic compound. Although there is an obvious need for an adapted posology in patients with liver diseases, only suggestions can be drawn from presently limited data.

Bile↗