Cimetidine induces hepatic heme oxygenase activity without altering hepatic heme catabolism

Cimetidine inhibits oxidative drug metabolism; it is not known whether this drug alters the catabolic fate of hepatic heme. We therefore investigated hepatic heme turnover both by a 14CO breath test and directly by labeling the heme pool. Neither acute (150 mg/kg i.p.) nor chronic (150 mg/kg i.p. bid for 3 days) cimetidine administration significantly affected hepatic heme turnover. Chronic, but not acute, cimetidine significantly (p less than 0.025) increased heme oxygenase activity. Cimetidine inhibited heme oxygenase activity in vitro at concentrations achieved in vivo.     

Cimetidine induces hepatic heme oxygenase activity without altering hepatic heme catabolism

Summary Cimetidine inhibits oxidative drug metabolism; it is not known whether this drug alters the catabolic fate of hepatic heme. We therefore investigated hepatic heme turnover both by a¹⁴CO breath test and directly by labeling the heme pool. Neither acute (150 mg/kg i.p.) nor chronic (150 mg/kg i.p. bid for 3 days) cimetidine administration significantly affected hepatic heme turnover. Chronic, but not acute, cimetidine significantly (p<0.025) increased heme oxygenase activity. Cimetidine inhibited heme oxygenase activity in vitro at concentrations achieved in vivo.     

Myofibroblasts in hepatic schistosomal fibrosis

Summary Myofibroblasts were identified in liver portal spaces of patients with Symmers' fibrosis following infection by Schistosoma mansoni.Acknowledgments. This research was supported by a grant from U.E.R. (Human Biology) Claude Bernard University, Lyon (France), and by the Conselho Nacional de Pesquisas (Brazil). Thanks are due to Mrs Pavans de Ceccatty for her skillful technical assistance.     

Mucopolysaccharides in experimental hepatic fibrosis

Résumé L'intoxication chronique au tétrachlorure de carbone produit dans le tissu hépatique du rat une forte augmentation des hexosamines et des sulfates liés sans modifier la teneur en acides uroniques. Ces modifications sont parallèles au processus de fibrilogénèse. Ces données indiquent l'accumulation pathologique d'un matériel de type glycosaminoglycan sulfaté.     

Temperature-dependence of stress-induced hepatic autophagy

Summary In rats, restraint for 48 h elicits hepatic glycogen depletion, autophagy and other ultrastructural changes (e.g. mitochondrial enlargement and rough endoplasmic reticulum disorganization) associated with marked hypothermia. By restoring the body temperature of these animals, all the hepatocytic alterations are abolished.Supported in part by the Medical Research Council of Canada (Block Term Grant MT-1829) and the Conseil de la recherche en santé du Québec. A preliminary report of this work was presented at the 19th Annual Meeting of the Canadian Federation of Biological Societies, Halifax, 15–18 June 1976.Recipient of a studentship from the Conseil de la recherche en santé du Québec.The authors thank Mr M. Audet, Mrs A. Perea and Miss F. Dionne, for their excellent technical assistance.     

Corticosteroid effect on hepatic collagens

Zusammenfassung Nach Cortison-Behandlung wird sowohl der Gehalt als auch die spezifische Aktivität des neutralen löslichen Kollagens in der Rattenleber vermindert. Die kollagenolytische Aktivität für das lösliche Kollagen vermehrt sich hingegen und zwar trotzdem die Aktivität für unlösliches Kollagen verändert blieb.     

Soluble hepatic lectin in regenerating liver

Summary Similar activity of a soluble hepatic lectin was measured in regenerating rat liver 12 h following partial, hepatectomy or gentle manipulation. Lectin response seems to be related to trauma rather than cell proliferation.     

The reticulo-endothelial localization of hepatic acetylcholinesterase

Zusammenfassung Die Acetylcholinesterase wurde histochemisch in den sinusoidal-reticulo-endothelialen Zellen der Kaninchenleber gefunden. Es wird angenommen, dass das Enzym an der Fett- und Esterumwandlung beteiligt ist.     

Cyclophosphamide-impaired regulation of hepatic heme metabolism

In male rats hepatic cytochromes b5 and P-450 were reduced at different times after treatment with cyclophosphamide (CP) (200 mg/kg i.p. for 3 days). In contrast, microsomal heme did not change until 48 h after the last dose of CP, leading to accumulation of heme in a 'non-cytochromal' form. Parallel to the above changes the heme metabolism showed derangement: delta-aminolaevulinate synthase, the rate-limiting enzyme in heme synthesis, was depressed and heme oxygenase, the enzyme which catalyzes the oxidative degradation of heme, was increased.     

Chlorinated benzene induction of hepatic porphyria

Summary 1,4-Dichlorobenzene and 1,2,4-trichlorobenzene were compared with hexachlorobenzene which is known to cause porphyria. Although hexachlorobenzene administration resulted in a manyfold increase in liver porphyrin levels and urinary excretion of porphyrins, the lesser chlorinated compounds did not do so.Supported by grant R804328 from the US Environmental Protection Agency.     

Mechanism of allyl alcohol-induced hepatic necrosis

Résumé Ces recherches indiquent que la répartition des lésions nécrotiques produites chimiquement peut être déterminée par la localisation intrahépatique d'enzymes métabolisant les drogues, enzymes qui synthétisent, dans les cellules où ils sont produits, les métabolites chimiquement actifs capables d'alkylation des macromolécules

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I thank Mr.John George, MissKathy Lalush and Mrs.Mary Alice Larson for their expert technical assistance.     

Cyclophosphamide-impaired regulation of hepatic heme metabolism

Summary Im male rats hepatic cytochromes b₅ and P-450 were reduced at different times after treatment with cyclophosphamide (CP) (200 mg/kg i.p. for 3 days). In contrast, microsomal heme did not change until 48 h after the last dose of CP, leading to accumulation of heme in a non-cytochromal form. Parallel to the above changes the heme metabolism showed derangement: -aminolaevulinate synthase, the rate-limiting enzyme in heme synthesis, was depressed and heme oxygenase, the enzyme which catalyzes the oxidative degradation of heme, was increased.     

Brominated benzene induction of hepatic porphyria

Summary Unlike the highly porphyrinogenic fungicide hexachlorobenzene, hexabromobenzene was a poor inducer of porphyria. Similarly, 1,2-dibromobenzene and 1,2,4-tribromobenzene, while causing small increases in hepatic porphyrins, did not increase ALA synthetase or the urinary excretion of porphobilinogen (PBG), aminolevulinic acid (ALA) or porphyrins.Supported by grant R805070 from the US Environmental Protection Agency.     

Effect of vasectomy on hepatic drug metabolism

2 months after bilateral vasectomy the metabolism of aniline but not aminopyrine was increased in rat liver homogenates, whereas vasectomy did not affect the metabolism of either compound in guinea-pig liver homogenates.     

Effect of vasectomy on hepatic drug metabolism

Summary 2 months after bilateral vasectomy the metabolism of aniline but not aminopyrine was increased in rat liver homogenates, whereas vasectomy did not affect the metabolism of either compound in guinea-pig liver homogenates.Supported by a grant from the University of Nebraska Medical Center.