Search PubMed⌕ Search

Biomedical subjects

G Poli

Publications and source records attributed to G Poli.

At least 271 records · Page 15Linked to original sources
PubMed1984

Toxicity of 1,2-dibromoethane in isolated hepatocytes: role of lipid peroxidation.

Treatment of isolated hepatocytes with 1,2-dibromoethane (DBE) caused a concentration dependent depletion of cellular glutathione (GSH) content and a parallel increase in the covalent binding of reactive intermediates to cell proteins, as a consequence of the haloalkane activation. The reduction of the hepatocyte GSH content, induced by DBE, stimulated the onset of lipid peroxidation, as measured by malondialdehyde (MDA) accumulation. N-Acetylcysteine (1 mM) was found to partially prevent GSH loss and to inhibit MDA formation, whereas equal concentrations of cysteine and methionine were ineffective on these respects. The stimulation of the peroxidative reactions appeared to be also associated with an increase in the leakage of lactate dehydrogenase (LDH) from the cells, indicative of a severe hepatocyte injury. Antioxidants such as alpha-tocopherol, N,N'-phenyl-phenylenediamine (DPPD) and promethazine, as well as N-acetylcysteine reduced MDA formation to various extents and also protect against LDH release, yet without interfering with the covalent binding of DBE reactive intermediates to hepatocyte proteins. These results suggest the involvement of lipid peroxidation, consequent to GSH depletion, in the pathogenesis of liver cell necrosis due to DBE.

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↗
PubMed1984

Further experiments on lipid peroxidation in transplanted and experimental hepatomas.

The results of experiments on the subject of lipid peroxidation in hepatomas are described. It is now clear that lipid peroxidation is strongly decreased in most highly dedifferentiated hepatomas. It seems evident that the extent of the decline is strictly related to the degree of dedifferentiation. The model of diethylnitrosamine carcinogenesis, according to the method by Solt, Medline and Farber, has been now adopted to study the stages of carcinogenesis. It was shown that a net decline in lipid peroxidation occurs as early as at the stage of reversible nodules and progresses until the development of clear hepatomas. This change is practically simultaneous with a decline in the efficiency of the enzymes of the drug metabolizing system and in the content of cytochrome P450-Glutathione content and metabolism show also important changes. In fact, a dramatic increase in gamma-glutamyl-transpeptidase takes place very early during carcinogenesis, and is responsible for large decline in total glutathione during incubation of the homogenates. Glutathione peroxidase activity, on the contrary, is decreased, whereas glutathione reductase does not show significant changes. The supernatant of highly anaplastic tumors inhibits lipid peroxidation in normal liver homogenates, suggesting the presence of substances provided with antioxidant properties. These cannot be, however, related to a higher glutathione content. Supernatants from early nodules seem to be unable to block lipid peroxidation in normal liver homogenates. Preliminary experiments done to study the aldehyde pattern produced during lipid peroxidation, both in hepatomas and in nodules, confirm the presence of very poor lipid peroxidation and possibly of different peroxidation kinetics.

Aminopyrine N-Demethylase↗
PubMed1984

Cell-mediated cytotoxicity to autologous hepatocytes in HBsAg positive liver disease: an analysis of the killing specificity and of the clinical use of the test.

The specificity of a system measuring cell-mediated cytotoxicity as effector-induced target cell detachment from plastic recently adopted to study autologous hepatocyte killing in liver disease, was examined in 17 HBsAg positive liver patients whose hepatocytes (after biopsy digestion with collagenase) were incubated in Terasaki plates with the corresponding blood lymphocytes over two days. The hepatocyte viability and the specificity of the effectors were evaluated as determinants of the clinical value of the test. We found that: (a) hepatocytes in all experiments showed membrane damage owing to the lytic action of collagenase on the small liver core; (b) patients' lymphocytes detached diseased autologous hepatocytes more efficiently than did normal lymphocytes with healthy hepatocytes; (c) in eight patients cytotoxicity appeared equally distributed between a population enriched in T cells and one enriched in non-T cells; yet the mean cytotoxic index of the latter subset was higher than that of the former; (d) cytotoxicity was not blocked by the addition of either aggregated IgG or purified HBsAg; (e) protein synthesis seemed required to promote hepatocyte detachment, for lymphocytes treated with Actinomycin D were no longer active. Poor target viability detracts from the specificity and the clinical value of the test, that therefore turns out to be a major problem of liver cell culture.

Adolescent↗
PubMed1983

[Pharmacology of lycorine. 1) Effect on biliary secretion in the rat].

The Authors study pharmacological actions of lycorine, alkaloid of Lycoris radiata. On the basis that anti-inflammatory substances have a choleretic effect, the activity of lycorine on biliary secretion of rats has been investigated. Lycorine, at a dose of 1 mg/kg induces, in rats anaesthetized with urethane (1,2 g/kg i.m.), a marked choleretic effect. This experiment do not define the mechanism responsible for the observed choleresis.

Amaryllidaceae Alkaloids↗
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

Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes.

1. Methods using t.l.c. and high-pressure liquid chromatography (h.p.l.c.) have been used to separate the complex variety of substances possessing a carbonyl function that are produced during lipid peroxidation. 2. The major type of lipid peroxidation studied was the ADP-Fe2+-stimulated peroxidation of rat liver microsomal phospholipids. Preliminary separation of the polar and non-polar products was achieved by t.l.c.: further separation and identification of individual components was performed by h.p.l.c. Estimations were performed on microsomal pellets and the supernatant mixture after incubation of microsomes for 30 min at 37 degrees C. 3. The polar fraction was larger than the non-polar fraction when expressed as nmol of carbonyl groups/g of liver. In the non-polar supernatant fraction the major contributors were n-alkanals (31% of the total), alpha-dicarbonyl compounds (22%) and 4-hydroxyalkenals (37%) with the extraction method used. 4. Major individual contributors to the non-polar fraction were found to be propanal, 4-hydroxynonenal, hexanal and oct-2-enal. Other components identified include butanal, pent-2-enal, hex-2-enal, hept-2-enal, 4-hydroxyoctenal and 4-hydroxyundecenal. The polar carbonyl fraction was less complex than the non-polar fraction, although the identities of the individual components have not yet been established. 5. Since these carbonyl compounds do not react significantly in the thiobarbituric acid reaction, which largely demonstrates the presence of malonaldehyde, it is concluded that considerable amounts of biologically reactive carbonyl derivatives are released in lipid peroxidation and yet may not be picked up by the thiobarbituric acid reaction.

Adenosine Diphosphate↗
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

Bluetongue virus: comparative evaluation of enzyme-linked immunosorbent assay, immunodiffusion, and serum neutralization for detection of viral antibodies.

Comparative studies on the detection of bovine serum immunoglobulin G antibodies to bluetongue virus with an enzyme-linked immunosorbent assay, an immunodiffusion method, and a serum neutralization assay demonstrated complete concordance between the enzyme-linked immunosorbent assay and the serum neutralization assay results. However, the immunodiffusion method failed to detect bluetongue virus antibody in a substantial number of sera found to possess bluetongue virus immunoglobulin G with the enzyme-linked immunosorbent assay.

Animals↗
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↗
PubMed1982

The fecal microbial population in the irritable bowel syndrome.

The focal microbial flora composition has been studied in patients affected by irritable bowel syndrome. The statistical analysis of the results showed a decrease of coliforms, lactobacilli and, to a lesser extent, bifidobacteria, as compared to control healthy individuals. Hypotheses on the cause of these modifications and their role in the maintenance and severity of the disease are discussed.

Bacteria↗