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Biomedical subjects

E Chiarpotto

Publications and source records attributed to E Chiarpotto.

At least 55 records · Page 3Linked to original sources
PubMed1987

Some biological effects of calvatic acid and its analog on isolated hepatocytes.

Calvatic acid is a new antibiotic with both a carboxylic group and an azoxy function in the benzene ring. The relationship between structure and biological activity in this substance and one of its analog, phenylazoxyxyanide, was investigated. Isolated hepatocytes were used as an experimental system: the release of lactate dehydrogenase and the colchicine-binding activity of tubulin were first evaluated; effects were dose and time dependent. micromolar concentrations of these drugs determined a significant decrease of the glucose-6-phosphatase activity and a slight inhibition of aminopyrene demethylation. A toxic effect at the microsomal level and an interaction with the microtubular system are thus possible.

Aminopyrine N-Demethylase↗
PubMed1986

Resistance to oxidative stress by hyperplastic and neoplastic rat liver tissue monitored in terms of production of unpolar and medium polar carbonyls.

The susceptibility of rat liver tissue to oxidative stress during its neoplastic transformation was analyzed by both qualitative and quantitative measurements of the carbonyl products of lipid peroxidation. Diethylnitrosamine was used as initiating agent of hepatocarcinogenesis and lipid peroxidation levels were monitored in the homogenates from normal liver, hyperplastic nodules and tumour, incubated in the presence or in the absence of ascorbate or adenosine diphosphate-iron complex. While the basal levels of lipid peroxidation in the three experimental conditions were found to be quite similar, in the presence of the pro-oxidant stimulus a remarkable reduction in aldehyde production was shown not only by the hepatoma tissue but also by the preneoplastic nodules.

Aldehydes↗
PubMed1986

Age related changes of glucagon binding and activity in isolated rat hepatocytes.

Hepatocytes isolated from young and old rats were compared for glucagon binding and its biological effect. Liver cells from young rats showed a receptor binding of the hormone significantly higher than cells from old rats. Such a behaviour was paralleled by the activity of the hormone. In fact, the glucagon-dependent stimulation of adenylate cyclase in the hepatocytes from the former group of animals was twice as high as in the latter.

Adenylyl Cyclases↗
PubMed1985

Carbon tetrachloride-induced inhibition of hepatocyte lipoprotein secretion: functional impairment of Golgi apparatus in the early phases of such injury.

Functional change of liver Golgi apparatus during carbon tetrachloride (CCl4) poisoning was demonstrated both in rat isolated hepatocytes and in the whole animal. The "in vitro" experimental model provided evidence of Golgi derangement early after giving the haloalkane. The "in vivo" analyses also showed that such an alteration involves both formative and secretory sides of the subcellular structure.

Animals↗
PubMed1984

Induction of cytochrome(s) P450-dependent drug metabolism in cultured MH1C1 hepatoma cells.

A cell line derived from a Morris hepatoma, MH1C1, was examined for its in vitro expression of monooxygenases. These cells were found to contain different forms of cytochrome P450, as shown by the response to inducers, namely phenobarbital (PB), 3-methylcholanthrene (MC) and metyrapone (MP). MH1C1 cell monolayers exposed to PB or MC showed an increase in the concentration of two spectrally distinct forms of cytochrome P450. The PB and MC treatments elicited enzyme activities towards the substrates aminopyrine and benzo(a)pyrene, respectively. The cell treatment with metyrapone led to a simultaneous stimulation of aminopyrine demethylase and benzo(a)pyrene hydroxylase activities, so underlining the peculiar features of this inducer.

Animals↗
PubMed1984

Studies on fatty liver with isolated hepatocytes. III. Cumene hydroperoxide-induced change of several cell functions.

Isolated rat hepatocytes have been treated with cumene hydroperoxide at concentrations not inducing irreversible cell damage. Under these experimental conditions cells show an enhanced lipid peroxidation, a decrease of glucose-6-phosphatase activity and of cytochrome P-450 content, and a stimulation of aminopyrene demethylation. Furthermore, the hepatocyte incorporation of amino acids is slightly but significantly reduced by the tested compound. Finally, because of the inhibitory effect of cumene hydroperoxide on cell lipoprotein but not on protein secretion, a mechanism of damage acting at the level of the assembly and maturation of lipoprotein micelles is postulated.

Aminopyrine↗
PubMed1983

In vitro evidence for CCl4 metabolites covalently bound to lipoprotein micelles.

CCl4-induced impairment of the lipoprotein secretion pathway of intact rat hepatocytes was carried out using 14CCl4 to check the possibility of binding to lipoproteins by CCl4 metabolites. After separation of different cell suspension fractions by means of ultracentrifugation and chemical precipitation procedures, a significant amount of the radioisotope was found covalently bound to the lipid and protein components of low density lipoproteins. Suitable experiments demonstrated that the bound radioisotope was represented by CCl4 metabolites and not by unactivated CCl4.

Animals↗
PubMed1983

Biochemical evidence for chemical and/or topographic differences in the lipoperoxidative processes induced by CCl4 and iron.

Isolated rat hepatocytes, treated with CCl4 or ADP-Fe3+ complex show an enhanced lipid peroxidation and a decreased glucose 6-phosphatase activity. Lipid peroxidation is much more stimulated by ADP-Fe3+ or Fe3+ than by CCl4, when the metal and the haloalkane are used at a similar concentration. Increasing rates of lipid peroxidation in the different experimental conditions do not correlate with the degree of glucose 6-phosphatase inactivation, which is produced by CCl4 and not by a similar amount of ferric iron. In the case of iron, its intracellular concentration must be higher to give the enzyme inactivation exerted by CCl4. Higher intracellular levels of iron are reached when the metal is added to the cell suspension together with ADP. Under these conditions there is inactivation of glucose 6-phosphatase. Possible mechanisms accounting for a different enzyme sensitivity to iron and CCl4 are discussed.

Adenosine Diphosphate↗
PubMed1983

Paracetamol-stimulated lipid peroxidation in isolated rat and mouse hepatocytes.

Treatment of isolated hepatocytes from 3-methylcholanthrene induced rats with 1 mM paracetamol has been found to greatly decrease cellular reduced glutathione (GSH) content and to promote lipid peroxidation, evaluated as malonaldehyde (MDA) production and conjugated diene absorbance. A similar dosing of hepatocytes from phenobarbital-induced or normal rats is ineffective in that respect. On the other hand, the aspecific stimulation of the cytochrome P-450-mediated paracetamol activation due to acetone addition further increases GSH depletion as well as MDA production. Isolated hepatocytes with basal low GSH content are also more susceptible to paracetamol-induced lipid peroxidation, indicating that the rate of the drug metabolism and the cellular GSH content are critical factors in the determination of such peroxidative attack. In isolated mouse liver cells paracetamol does not require preliminary cytochrome P-450 induction to stimulate MDA formation, even at concentrations ineffective in rat cells. However, 5 mM paracetamol, despite a great depletion of cellular GSH content, does not promote MDA formation either in the rat or in the mouse hepatocytes. This effect may be due to the ability of paracetamol to scavenge lipid peroxides under defined conditions, as tested in various lipid peroxidizing systems. Membrane leakage of lactate dehydrogenase (LDH) is evident in paracetamol treated cells undergoing lipid peroxidation, but not when MDA formation is inhibited by high doses of the drug or by addition of anti-oxidants such as alpha-tocopherol and diphenylphenylenediamine (DPPD). Nevertheless in these conditions the covalent binding of activated paracetamol metabolites is not affected, suggesting that lipid peroxidation might play a role in the pathogenesis of liver damage following paracetamol overdose.

Acetaminophen↗
PubMed1982

Functional impairment of intact rat liver cells due to biological aldehydes.

The addition of lipid peroxidation end-products, 4-hydroxynonenal (HNE) or hexanal (HEX) to the incubation medium of rat hepatocytes caused significant decrease of cell cytochrome P-450 content and inactivation of total cell glucose-6-phosphatase. Both the tested aldehydes exerted a marked inhibition of triglyceride secretion by liver cells. The reported results on intact cells furtherly support a possible damaging effect of aldehydes in pathological conditions in which a stimulation of lipid peroxidation occurs.

Aldehydes↗
PubMed1982

HPLC analyses of the aldehydic patterns produced during lipid peroxidation.

The peroxidative breakdown of membrane lipids leads to the production of several compounds with carbonyl functions. Their production has been monitored in rat liver homogenates treated with prooxidant agents namely vitamin C and ADP-Fe2+ complex. Preliminar HPLC separation of the unpolar and medium polar carbonyls produced, allowed the identification of few of them, in particular, hexanal and 4-OH-nonenal. The aim of this report is to underline the usefulness to integrate malonaldehyde evaluation with the analysis of the other carbonyls produced during lipid peroxidation.

Adenosine Diphosphate↗
PubMed1982

Enzymatic impairment induced by biological aldehydes in intact rat liver cells.

The addition of lipid peroxidation end-products, 4-hydroxypentenal (HPE), 4-hydroxynonenal (HNE) or hexanal (HEX) to the incubation medium of rat hepatocytes caused a significant decrease of cytochrome P-450 content and inactivation of total cell glucose-6-phosphatase. In particular, the two hydroxyalkenals exerted their inhibitory action at micromolar concentration. These results on intact cells further support a possible damaging effect of aldehydes in pathological conditions in which a stimulation of lipid peroxidation occurs.

Aldehydes↗
PubMed1981

Effect of aldehydes on polyamine metabolism. II. Methylglyoxal-induced changes in S-adenosylmethionine decarboxylase (SAMD) activity and RNA synthesis and degradation in isolated hepatocytes.

In isolated rat liver cells methylglyoxal (MeG) inhibits S-adenosylmethionine decarboxylase activity and RNA and protein synthesis; MeG also stimulated RNA degradation. The changes induced by MeG in RNA metabolism are partially prevented (in the case of RNA synthesis inhibition) or totally abolished (in the case of RNA degradation stimulation) by exogenous spermidine addition. This suggests the effects of MeG on RNA metabolism are dependent, at least in part, on SAMD inhibition.

Adenosylmethionine Decarboxylase↗
PubMed1981

Effect of aldehydes on polyamine metabolism. III. Inhibition of S-adenosyl methionine decarboxylase (SAMD) by CCl4 and by aldehydes produced during lipid peroxidation.

In isolated rat liver cells in which lipid peroxidation is stimulated by CCl4, a strong inhibition of S-adenosylmethionine decarboxylase (SAMD) activity occurs. Some purified aldehydes, which are produced during lipid peroxidation, are able to inhibit SAMD activity in Yoshida hepatoma cells. The most active aldehyde is hydroxypentenal (HPE). It inhibits by 50% SAMD activity at 0.5 mM concentration in entire hepatoma cells, or in hepatoma cell sap, and at 0.1 mM concentration in partially purified hepatoma cell sap fractions.

Adenosylmethionine Decarboxylase↗
PubMed1981

Effect of aldehydes on polyamine metabolism. I. Method used to determine CO2 produced "in vitro" in enzymatic reactions: its application in evaluation of S-adenosylmethionine decarboxylase (SAMD) activity.

In this paper the Authors describe a new method they have adopted (in studies reported in accompanying papers II and III) for measuring S-adenosylmethionine decarboxylase activity in entire cells and cell fractions. The new method is a general one for recovering and measuring labelled carbon dioxide formed "in vitro" during enzymatic reactions. It presents several advantages when compared to traditional methods.

Adenosylmethionine Decarboxylase↗
PubMed1981

Influence of lipid peroxidation on lipoprotein secretion by isolated hepatocytes.

Isolated rat liver cells have been exposed to 3 different lipid peroxidation-inducing agents, CCl4, FeCl3 and cumene hydroperoxide, and the rates of malonaldehyde production and of lipoprotein secretion have been compared. Results indicate that it is possible to induce a high degree of lipid peroxidation without inducing strong changes in lipoprotein secretion. Only in CCl4-poisoned hepatocytes is lipoprotein secretion strongly impaired. In this experimental condition, the effect of free radical scavengers, or inhibitors of lipid peroxidation, as well as the behavior of both lipid peroxidation and lipoprotein secretion, have been evaluated. Promethazine and propyl gallate prevented malonaldehyde production, but neither agent reduced covalent binding nor improved secretion. Menadione, on the contrary, besides inhibiting malonaldehyde production, decreased covalent binding and protected against the impairment of secretion. These data lead to the conclusion that covalent binding of CCl4 metabolites, rather than lipid peroxidation products, accounts for the derangement of lipoprotein secretion in CCl4-poisoned liver cells.

Animals↗