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Biomedical subjects

G Stramentinoli

Publications and source records attributed to G Stramentinoli.

At least 19 recordsLinked to original sources
PubMed1989

Effects of the novel antidepressant S-adenosyl-methionine on alpha 1- and beta-adrenoceptors in rat brain.

alpha 1- and beta-adrenoceptors were studied ex vivo in the brains of rats receiving repeated daily treatment with the standard antidepressant imipramine or the atypical antidepressant S-adenosyl-L-methionine (SAM), which has minimal effects on monoamine reuptake or turnover. Consistent with past studies, a decrease in the density of beta receptors at three weeks and an increase in the affinity of alpha 1 receptors for the agonist phenylephrine at one week of treatment was observed with imipramine. By comparison, an increase in the density of beta receptors and a decrease in the affinity of alpha 1 receptors for phenylephrine was observed at one week of treatment with SAM. These changes were no longer apparent at three weeks of treatment. The results suggest that treatment with SAM does lead to changes in adrenergic neurotransmission, but that down regulation of beta receptors or increased agonist affinity of alpha 1 receptors may not be necessary for the production of antidepressant effects.

Animals↗
PubMed1988

Reproductive toxicity studies of ademetionine.

S-Adenosyl-L-methionine sulphate-p-toluene sulphonate (ademetionine, SAMe), a donor of methyl groups, was examined for effects upon embryofoetal toxicity following both premating treatment and treatment during pregnancy and for peri- and post-natal toxicity in the rat at dosages of 0, 100, 200 and 400 mg/kg/d SAMe ion by subcutaneous or intravenous administration. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 10, 20 and 40 mg/kg/d SAMe by intravenous administration. Treatment was considered to be without adverse effect upon any of the reproductive parameters examined on either F0 or on the untreated F1 generations. There was no indication that treatment adversely affected the litter parameters including the incidences of malformations, anomalies and skeletal variants. Some slight changes in the activity of the F1 females derived from F0 animals given 400 mg/kg/d were considered to be of minimal importance. In contrast to the above, adverse effects upon the parents were noted at 400 mg/kg/d including local tissue reaction at the injection sites and retardation of body weight gain. In the intravenous studies some rigidity and dyspnoea were noted following administration. Following subcutaneous premating treatment there was also evidence of histopathological change to the kidney of the female rat. Increased water consumption was noted in this latter study and amongst females rearing offspring in the embryo foetal toxicity study in which the compound was administered intravenously. At the lower dosages administered to the rat some local tissue reaction was evident as was some retardation of body weight gain, minimal at the lowest intravenous dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1987

Pharmacologic aspects of S-adenosylmethionine. Pharmacokinetics and pharmacodynamics.

Several studies in animals have shown the efficacy of parenteral S-adenosylmethionine (SAMe) as an anti-inflammatory drug. In this article, data are reported on plasma kinetics, distribution, and metabolism of SAMe after oral administration since preference is given to oral dosage in the usual clinical practice. The results demonstrate the intestinal absorption of SAMe and its active metabolism. Experiments confirm the anti-inflammatory activity of the drug by the oral route. Results are also reported on the analgesic effect of SAMe.

Administration, Oral↗
PubMed1987

Biochemical and behavioural indices of striatal dopaminergic activity after 6-methyltetrahydropterin.

The biochemical effects of 6-methyltetrahydropterin (6-MPH4), a synthetic analogue of tetrahydrobiopterin (BH4), the hydroxylase cofactor, were investigated on striatal dopaminergic neurons in the rat. Although a single parenteral dose of 6-MPH4 (18 or 54 mg/kg) did not significantly increase the content of dopamine (DA) or its acidic metabolites, L-didrohyphenylanine (L-DOPA) accumulation after decarboxylase inhibition was evident in rats receiving 54 mg/kg of 6-MPH4. On the other hand, 6-MPH4 (18 mg/kg) potentiated the reserpine-induced DA metabolism as demonstrated by increased HVA levels. In a behavioural test, 6-MPH4 partially prevented haloperidol-induced catalepsy. BH4 concentrations could thus be subsaturating with respect to tyrosine hydroxylase (TH), particularly when the enzyme activity is stimulated and the results suggest that cofactor supply may have pharmacological significance.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Lack of mutagenic activity of ademetionine in vitro and in vivo.

Studies on the mutagenic activity of ademetionine (S-adenosylmethionine) tested in vitro at concentrations of 2 mg/sample and in vivo at doses up to 1500 mg/kg always gave negative responses. Moreover, a patent lack of abnormal methylated bases in the liver DNA of ademetionine-treated rats suggests that, if abnormal methylation occurs by exogenously administered ademetionine, the amount of formed methylated residues must be quite lower than that removable by the transmethylase enzymes responsible for the in vivo repair.

Animals↗
PubMed1986

Effect of the variations of S-adenosyl-L-methionine liver content on fat accumulation and ethanol metabolism in ethanol-intoxicated rats.

The protective effect of S-adenosyl-L-methionine against rat liver steatosis induced by chronic ethanol ingestion was investigated. S-Adenosyl-L-methionine given during ethanol treatment prevented steatosis and accelerated recovery from steatosis when given after ethanol withdrawal. It also caused a slight inhibition of blood ethanol consumption in both acutely and chronically intoxicated rats. About 30% inhibition of alcohol dehydrogenase, but not of the microsomal ethanol oxidation system, occurred in rats subjected to acute ethanol toxicity as well as in normal rats as a consequence of S-adenosyl-L-methionine treatment. A comparison between S-adenosyl-L-methionine and pyrazole, as concerns inhibition of ethanol oxidation and fat accumulation, revealed that a greater inhibition of ethanol metabolism by pyrazole was associated with incomplete prevention of steatosis, while a lower inhibition by S-adenosyl-L-methionine was coupled to a complete prevention. Ethanol induced a drastic decrease of reduced glutathione liver content as well as 630 and 133% increases of blood and liver acetaldehyde contents, respectively. S-Adenosyl-L-methionine treatment almost completely reconstituted the liver reduced glutathione pool and caused a large decrease of the liver and blood acetaldehyde contents. 1-Chloro-2,4-dinitrobenzene, which depletes the cellular reduced glutathione, and diethylethanolamine, an inhibitor of the phosphatidylethanolamine methylation, abolished the S-adenosyl-L-methionine-induced modifications of the reduced glutathione, acetaldehyde, and triacylglycerol contents in the liver of ethanol-treated rats. Neither S-adenosyl-L-methionine nor reduced glutathione inhibitors affected the liver acetaldehyde dehydrogenase activity. It is suggested that, although S-adenosyl-L-methionine induced a small inhibition of ethanol metabolism in the liver, its antisteatosic effect could largely depend on its role as a modulator of the reduced glutathione liver content.

Acetaldehyde↗
PubMed1985

Inhibition of lymphocyte function by a naturally occurring nucleoside: 5'-methylthioadenosine (MTA).

The link between immunodeficiencies and nucleoside metabolism is exemplified by the inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase which are associated with an abnormal development of the immune system. In this report we show that high doses of methylthioadenosine (MTA), a natural purine nucleoside, inhibit both the mitogen-induced blastogenesis of human peripheral blood lymphocytes (PBL) and the pokeweed mitogen (PWM)-driven in vitro immunoglobulin synthesis by PBL in a non-toxic and reversible fashion. Our data support the view that both T and B cells are sensitive to MTA inhibition and that PWM-driven Ig production is more affected by MTA than the mitogen-induced PBL proliferation. The observation that MTA causes an evident inhibition of in vitro PWM-driven Ig secretion when added four days after the start of the cultures suggests that MTA can exert its activity not only on proliferation but also on differentiation of B cells.

Adenosine↗
PubMed1985

S-adenosyl-L-methionine protection against alpha-naphthylisothiocyanate-induced cholestasis in the rat.

The effect of S-adenosyl-L-methionine (SAMe) on cholestasis induced by alpha-naphthylisothiocyanate (ANIT) was studied in rats. SAMe significantly attenuated both bile flow impairment and elevated values of serum bilirubin, glutamic pyruvic transaminase and alkaline phosphatase in ANIT-treated animals. These results suggest that SAMe protects the rat liver against the toxic effects of ANIT.

1-Naphthylisothiocyanate↗
PubMed1985

Anti-inflammatory activity of S-adenosyl-L-methionine in animal models: possible interference with the eicosanoid system.

In rats, the anti-inflammatory activity of parenteral S-adenosyl-L-methionine (SAMe) in carrageenin- and nystatin-induced oedemas and in carrageenin-induced pleurisy was tested. The capability of the drug to inhibit the production of PG-like material in sponge exudates and by peritoneal leukocytes during bacterial phagocytosis was also evaluated. Two of these experimental models were used to administer the compound by the oral route in order to see whether oral and injected SAMe had similar effects. The results obtained show that SAMe can exert anti-inflammatory activity by inhibiting the oedema and pleurisy in rats and PG-like material production in inflammatory exudates and in the phagocytosis process by leukocytes. The mechanism of action of SAMe is discussed.

Animals↗
PubMed1979

[The effect of S-adenosyl-L-methionine (SAM) on membrane permeability in the perfused rat liver].

S-adenosilmethionine is present in most human tissues and is an important factor for transmethylation, transulphuration and aminopropylation reactions. The compound improves the biological, morphological and histochemical aspects of rat liver following CCl4 intossication. At the same time has been successfully used during chronic liver disease in man. With the aim to better clarify the action mechanism of SAMe some aspects concerning its effects on cell permeability in rat liver, by using the perfusion technique, have been investigated. In particular the capacity of this compound to prevent the enzymatic loss (GPT and GOT) during liver perfusion has been studied. 30 perfusions without SAMe, as control, and 6 by infusing 2 mg of compound during the perfusion time have been accomplished. Varing the perfusion time from 0 to 120 min it has been observed that at any time the presence of the SAMe reduced by about 50% the loss of GOT. Similarly the activity of GPT ranging from 2 to 6 mU/ml indicate that no appreciable enzyme output occurs in presence of SAMe.

Animals↗
PubMed1979

Methylation hypothesis.

L-Methionine had no behavioral effects in normal humans and failed to increase concentrations of S-adenosylmethionine (methyl donor) in human or rat blood, while increasing rat liver levels more than fivefold. Methionine or S-adenosylmethionine in very high doses had almost no effect on methylation of tritiated levodopa in rodent tissues; various "methyl acceptor" molecules, including nicotinamide, guanidineacetic acid, and estradiol similarly had little effect. In rabbit lung, methionine and S-adenosylmethionine not only failed to increase production of dimethyltryptamine, but actually decreased it, possibly due to end-product inhibition by S-adenosylhomocysteine, which also strongly inhibited methylation of dopa in rat. These results fail to support several predictions of the "methylation hypothesis" concerning the pathophysiology and potential treatment of idiopathic psychotic disorders and leave the consistent clinical worsening effects of methionine in schizophrenia unexplained.

Adult↗
PubMed1979

Localization of S-[methyl-14 C]adenosyl-L-methionine in pregnant mice and fetuses as determined by autoradiography.

The distribution of S-[methyl-14C]Adenosyl-L-methionine has been examined in pregnant mice using an autoradiographic technique. The results indicate that the compound crosses the placental barrier quite slowly and accumulates in some fetal tissues such as intestine, liver, kidney, eye and lung. The highest concentration is reached 12 hours after i.v. administration of the compound. In the placenta the labelling can be detected for a long time after administering the radioactive compound.

Animals↗
PubMed1979

Kinetics of S-adenosyl-L-methionine in isolated perfused rat liver and its effects on microsomal enzyme activity.

S-Adenosyl-L-methionine (SAMe) levels in liver tissue were reduced by 35% after isolation and washing of the organ. The apparent half-life of SAMe (1,75-25 microM) during liver perfusion was between 120 and 460 min; however the uptake of the labelled methyl group by hepatic tissue of fed rats was low (6%). This value increased to 12% in organs isolated from 24-hour fasted animals. Addition of SAMe to the perfusion medium increased tissue levels of ATP. Except for N-demethylation of aminopyrine and cytochrome c reductase, liver microsomal activity was not affected by treatment with SAMe either in vivo or/and in perfused liver.

Adenosine Triphosphate↗
PubMed1979

Intestinal absorption of S-adenosyl-L-methionine.

The gastrointestinal absorption of S-adenosyl-L-methionine (SAMe) is demonstrated by evaluating plasma levels and gastrointestinal content of the unmodified molecule after oral administration. When [methyl-14C]SAMe is given orally, the radioactivity found in the liver is associated both with SAMe and phosphatidylcholine, a compound known to be derived from the methylation of phosphatidylethanolamine with SAMe as a methyl donor. These results and low plasma levels after the oral administration may be suggestive of a first-pass effect of SAMe characterized by an extensive uptake of the drug by the liver where it is rapidly metabolized.

Administration, Oral↗