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M Aragno

Publications and source records attributed to M Aragno.

51 records · Page 3Linked to original sources
PubMed1992

In vivo studies on halogen compound interactions. IV. Interaction among different halogen derivatives with and without synergistic action on liver toxicity.

The liver toxicity of several halogen compound mixtures have been tested. The compounds were selected on the basis of their metabolic pathways: carbon tetrachloride (CT) and trichlorobromomethane (TCBM) undergo a dehalogenation via P450-dependent enzyme system, 1,2-dichloroethane (DCE) and 1,2-dibromoethane (DBE) are mainly conjugated with the cytosolic glutathione (GSH) by means of the GSH-S-transferase. The mixture TCBM+DBE shows a more than additive action on lipid peroxidation and liver necrosis. TCBM, like CT, reduces the hepatic level of GSH-S-transferase, increasing the amount of DBE available for cytochrome P450-dependent metabolism, with the production of toxic metabolites. Thus, the behavior of the mixture TCBM+DBE is very similar to that of the mixture CT+DBE, previously reported. Mixtures composed of CT+TCBM and DCE+DBE do not show any synergistic effect on liver toxicity. The results allow one to conclude that the toxicity of mixtures of halogen compounds can be partly predicted on the basis of their metabolic pathways. When the metabolism is quite different, a synergistic toxicity can occur if one pathway interferes with a detoxification mechanism of the other compound. If the two metabolisms are very similar they produce, at most, an additive toxicity.

Alanine Transaminase↗
PubMed1991

Lipid peroxidation and irreversible cell damage: synergism between carbon tetrachloride and 1,2-dibromoethane in isolated rat hepatocytes.

The combination of 1,2-dibromoethane (DBE) with carbon tetrachloride (CCl4) in the isolated rat hepatocyte model produces a significant potentiation of both lipid peroxidation and plasma membrane damage induced by the latter compound. The increase in malondialdehyde production precedes the hepatocyte damage, evaluated in terms both of lactate dehydrogenase leakage and trypan blue exclusion. When hepatocytes are isolated from vitamin E pretreated rats, both the prooxidant and the cytotoxic effects of CCl4 are prevented. Also the synergism between CCl4 and DBE on lipid peroxidation disappears completely while that on cell damage is strongly reduced. The increased lipid peroxidation appears to be one of the mechanisms of the observed synergism between CCl4 and DBE on hepatocyte damage. Regarding the antioxidant status of the hepatocyte challenged with CCl4 and DBE, an early and significant consumption of vitamin E is observed only in the presence of the mixture of these xenobiotics. Total nonprotein thiol content is not significantly modified by CCl4 poisoning while DBE, alone and in association with CCl4, markedly decreases it. Vitamin E supplementation does not prevent but moderately delays total nonprotein thiol depletion due to DBE or to the mixture. Finally, glutathione transferase activity is significantly reduced by CCl4 treatment and not by DBE, and vitamin E supplementation totally prevents such inhibition. The increased prooxidant effect of CCl4 plus DBE compared to CCl4 alone seems related to the shift in DBE metabolism consequent to the CCl4-dependent inactivation of glutathione transferase.

Animals↗
PubMed1989

In vivo studies on halogen compound interactions. II. Effects of carbon tetrachloride plus 1,2-dibromoethane on relative liver weight and hepatic steatosis.

A mixture of carbon tetrachloride (CCl4) and 1,2-dibromoethane (DBE) results in a significant increase in relative liver weight (RLW) when compared with the effect of each substance individually. At the same time, the liver triglyceride levels of rats treated with the mixture are lower than in those treated with CCl4 alone. This increase in RLW is not caused by simple tissue oedema. Lipoprotein secretion and the concentration of circulating non esterified fatty acids (NEFA) are not involved in the DBE-induced reduction of steatosis provoked by CCl4. The synthesis of triglycerides is significantly depressed in animals treated with the mixture. These findings provide further evidence of the previously observed enhancement of liver toxicity caused by the simultaneous presence of both agents, since the apparent protection against steatosis is due to greater damage to the liver cell, which is no longer able to counter the steatogenic action of CCl4 through a sufficient synthesis of triglycerides.

Animals↗
PubMed1988

In vivo studies on halogen compound interactions. I. Effects of carbon tetrachloride plus 1,2-dibromoethane on liver necrosis.

Investigation of the hepatotoxicity of a mixture of two halogen compounds--carbon tetrachloride (CT) and 1,2-dibromoethane (DBE) used in association, especially in agriculture--is reported. Their simultaneous administration in the rat potentiates the necrosis provoked by exposure to CT alone. This damage can be totally prevented by prior treatment with vitamin E, which raises the liver antioxidant level. Determination of the TBA-reacting substances released from the liver homogenates of animals treated with one or both substances also corroborates the importance of lipid peroxidation in the pathogenesis of this potentiation. Furthermore, no significant difference between poisoning by CT and CT + DBE is noted when liver GSH values are measured under the same experimental conditions. This finding rules out the possibility that potentiation is only the simply sum of the damage caused by the two compounds (lipid peroxidation due to a radical initiator for CT, depletion of GSH for DBE). It is thus something more than a mere combination of two mechanisms of action and further investigation is required to unravel its more complex pathogenesis.

Animals↗
PubMed1988

Experimental studies on the toxicity of Ferula communis in the rat.

The study of two chemically characterized varieties of Ferula communis showed that only plants containing prenylated coumarins are toxic. The contrasting data on the toxicity of Ferula communis most probably raised from the use of chemically uncharacterized specimens. Among the constituents of the toxic variety, both ferulenol, a 4-hydroxycoumarin derivative, and ferprenin, a pyrane (3,2-c) coumarin derivative, affected blood clotting. No hepatotoxicity was elicited by these two compounds.

Animals↗
PubMed1986

A model for monitoring changes in liver function.

An experimental model for monitoring rat liver function during protracted exposure to hepatotoxic agents is proposed. Owing to their invasiveness, the models usually employed are appropriate for studying the mechanism of action of toxic substances, but do not allow the liver situation to be followed over the course of time. The need to sacrifice animals to determine liver triglycerides-one of the key parameters in the progress of toxic damage- reduces the possibility of following such progress in the same animals. This study describes the testing of a model for monitoring three basic parameters of liver injury: cytolysis, steatosis and metabolic deficiency of the liver. CCl4 has been chosen as model-hepatotoxin. Steatosis is determined by evaluating the triglyceride content of small specimens of liver, obtained through open-field biopsies, which appear to be representative of the whole liver. Fatty liver is paralleled by the block in Triton-induced hypertriglyceridaemia. Determination of serum triglycerides derives from a very poorly invasive technique which can be repeated several times. The combination of these tests with the assessment of both the cytolysis (ALT and SDH release into the circulation) and the impairment of the efficiency of liver microsomal enzymes (TMO clearance), seems to offer a reliable experimental procedure in predicting the hepatotoxic effect of xenobiotics.

Animals↗
PubMed1983

Production and consumption of hydrogen in a eutrophic lake.

The vertical distribution of hydrogen was measured in the Loclat, a eutrophic and holomictic lake near Neuchâtel, Switzerland, before and during summer stratification. H(2) concentrations decreased with depth in the anaerobic hypolimnion and were often below the detection limit (2.5 nl of H(2) liter) in the water adjacent to the lake sediment. H(2) was apparently not released from the lake sediment. The highest H(2) concentrations (>4 mul of H(2) liter) were observed in the aerobic water of the epilimnion and metalimnion. There, the H(2) concentrations changed with time, indicating a turnover of H(2). The H(2) production processes could not be studied in the laboratory since incubation of water samples in light or darkness did not result in H(2) production but rather always in H(2) consumption. The possible role of cyanobacteria and algae for H(2) production is discussed. Aerobic or anaerobic H(2) consumption activities were observed at all depths of the water column, with highest activities in the hypolimnion. Aerobic H(2) consumption activity was insensitive to azide inhibition, but sensitive to heat, mercuric chloride, or cyanide. It was restricted to a particle fraction of 0.2 to 3.0 mum in size, so that it must be due to single bacterial cells. Aerobic hydrogen bacteria, on the other hand, occurred in clusters of >3.0 mum. Therefore, the hydrogen bacteria could not have caused the H(2) consumption in lake water. The aerobic H(2) consumption activity followed Michaelis-Menten kinetics, with a K(m) of 67 nM H(2). This is an exceptionally low value compared with K(m) values of hydrogenases in hydrogen bacteria and other species, but is similar to that for H(2)-decomposing abiontic soil hydrogenases.

Journal Article↗
PubMed1980

Effect of a fast-growing ascites hepatoma (Yoshida AH-130) on proteinase activities in the rat liver.

The weight of the liver and its DNA content definitely increase in rats transplanted with the ascites hepatoma AH-130 (Yoshida). The specific activity of cathepsin B1 decreases progressively in the liver during the first week after transplantation reaching one third of the initial levels, whereas that of cathepsin D shows the opposite behaviour increasing to levels 40% higher than in controls. The activity of the two proteinases in the blood plasma varies in a similar way, though the modifications are even more pronounced than in the liver. The relevance of the changes in tissue proteinase activities to the liver growth in tumour-bearing animals is discussed.

Animals↗
PubMed1977

Micromorphology of Gram-negative hydrogen bacteria. I. Cell morphology and flagellation.

The cell morphology, the arrangement and fine structure of flagella and the piliation of the following Gram-negative aerobic hydrogen bacteria have been studied: Alcaligenes eutrophus, Alcaligenes paradoxus, Alcaligenes ruhlandii, Pseudomonas flava, Pseudomonas pseudoflava, Pseudomonas palleronii, Pseudomonas facilis, Aquaspirillum autotrophicum, Paracoccus denitrificans, Corynebacterium autotrophicum, and strains MA 2 and SA 35. The identity of the bacteria was examined by their substrate spectra and type of flagellation. Three types of flagellar fine structure were differentiated. The presence of pili was noted in strains of Alcaligenes paradoxus, Pseudomonas flava, P.pseudoflava, P.palleronii, and P.facilis.

Alcaligenes↗
PubMed1977

Micromorphology of Gram-negative hydrogen bacteria. II. Cell envelope, membranes, and cytoplasmic inclusions.

The fine structure of the cell envelope, of membrane systems and of cytoplasmic inclusions of Gram-negative aerobic hydrogen bacteria has been studied. The results have been tabulated, and three main groups could be recognized: Group 1: Alcaligenes eutrophus, A.paradoxus, A.ruhlandii, Pseudomonas facilis, P.flava, P.pseudoflava, P.palleronii, and Aquaspirillum autotrophicum; Group 2: "Corynebacterium" autotrophicum and strains MA 2 and SA 35; Group 3: Paracoccus denitrificans. Special structures related to the chemoautotrophic way of life of the hydrogen bacteria were not observed.

Alcaligenes↗
PubMedDate not supplied

Prevention of carbon tetrachloride-induced lipid peroxidation in liver microsomes from dehydroepiandrosterone-pretreated rats.

Dehydroepiandrosterone (DHEA), a lipid soluble steroid, administered to rats (100 mg/kg b.wt) by a single intraperitoneal injection, increases to twice its normal level in the liver microsomes. Microsomes so enriched become resistant to lipid peroxidation induced by incubation with carbon tetrachloride in the presence of a NADPH-regenerating system: also the lipid peroxidation-dependent inactivation of glucose-6-phosphatase and gamma-glutamyl transpetidase due to the haloalkane are prevented. Noteworthy, the liver microsomal drug-metabolizing enzymes and in particular the catalytic activity of cytochrome P450IIE1, responsible for the CCl4-activation, are not impaired by the supplementation with the steroid. Consistently, in DHEA-pretreated microsomes the protein covalent binding of the trichloromethyl radical (CCl3 degrees), is similar to that of not supplemented microsomes treated with CCl4. It thus seems likely that DHEA protects liver microsomes from oxidative damage induced by carbon tetrachloride through its own antioxidant properties rather than inhibiting the metabolism of the toxin.

7-Alkoxycoumarin O-Dealkylase↗
PubMedDate not supplied

Dehydroepiandrosterone inhibits the growth of DMBA-induced rat mammary carcinoma via the androgen receptor.

Dehydroepiandrosterone (DHEA) exerts opposite effects on the growth of mammary carcinoma. A stimulatory effect is observed in absence of estrogens, due to interaction of DHEA metabolite(s) with the estrogen receptor (ER); by contrast, in presence of estrogens DHEA inhibits tumor growth. The mechanism underlying the latter DHEA effect, which might be related to activation of the androgen receptor (AR), is poorly understood. Focusing on this point, we measured over a 20 days period the areas of DMBA-induced mammary tumors in rats given DHEA and/or the anti-androgen flutamide (FLU). Results show that DHEA inhibitory effect on the growth of mammary carcinoma is no longer observed when the ARs are blocked by FLU. Data are consistent with an involvement of ARs in the inhibitory effect of DHEA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Opposite effects of dehydroepiandrosterone on the growth of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas.

The effect of dehydroepiandrosterone (DHEA) (2 mg, twice daily p.o.) on the growth of the dimethylbenz (a) anthracene (DMBA)-induced mammary carcinoma was studied in intact and ovariectomized adult female rats. DHEA treatment stimulated the tumor growth in ovariectomized animals. Conversely, the tumors of intact rats treated with DHEA progressed to a lesser extent than those of intact untreated animals (p < 0.01). Plasma levels of DHEA were higher in DHEA-fed than in untreated animals (p < .01), whereas E2 concentrations were unchanged after DHEA administration. Estrogen receptor (ER) concentrations in tumor tissue of ovariectomized animals given DHEA were no different form those found in intact rats, whereas ER were undetectable in untreated ovariectomized rats. The data indicate that DHEA stimulates the growth of DMBA-induced mammary tumors in ovariectomized rats, while it reduces the tumor progression in intact animals.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

[Comparative activity of dibekacin and several cephalosporins on Pseudomonas aeruginosa].

Dibekacin is a semisynthetic aminonglycoside derivative of kanamicin B, with highly activity against most gram-positive and gramnegative bacteria. It is also active against bacteria relatively resistant to other antibiotics. Since Pseudomonas aeruginosa seems to be the most common strain recent clinical isolated, we compared the in vitro activity of dibekacin with other eigh cephalosporins against 579 clinical isolates of sensitive and gentamicin-carbenicillin resistant Pseudomonas aeruginosa. The results indicate that dibekacin was more active than any of the other antibiotics tested against all the organisms tested, including carbenicillin-resistant Pseudomonas aeruginosa.

Cefamandole↗