Visual evoked potentials were utilized to examine the neuronal transmission changes provoked by galactosamine-induced hepatic encephalopathy and by administration in normal animals of toxins presumably involved in the pathogenesis of hepatic encepalopathy. Separate acute administrations of ammonia, dimethyldisulfide, and octanoic acid induced lethargy, convulsions in the case of the first two, and coma with visual-evoked potential patterns that never resembled the evoked potentials recorded in hepatic coma. By contrast, single and repeated administrations of the three above-mentioned toxins together at lower doses induced lethargy and coma with visual-evoked potential patterns similar to those observed in galactosamine-induced hepatic coma. These observations, together with previously published data, are consistent with the concept that the synergistic interaction of these toxins plays a significant role in the pathogenesis of hepatic encephalopathy.

Ammonia↗

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Blood-brain barrier permeability to gamma-aminobutyric acid in hepatic encephalopathy.

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Blood-Brain Barrier↗

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Anti-inflammatory activity of newly synthesized 2,6-bis-(1,1-dimethylethyl)phenol derivatives.

Four new 2,6-bis-(1,1-dimethylethyl)phenol derivatives were synthesized and evaluated for their anti-inflammatory activity, in comparison with indomethacin and vitamin E, using the carrageenan paw oedema assay in rats. Among the tested compounds, the 4-(6,7-dichloro-4H-1,2,4-benzothiadiazine-3-yl)-2,6-bis-(1,1- dimethylethyl)-phenol-S,S-dioxide (4) was the most active compound markedly reducing oedema formation. Moreover compound 4 potentiated, particularly in the early phase of carrageenan paw swelling (2-4 h), the antiphlogistic effect of indomethacin. This compound, on the other hand, did not show ulcerogenic activity at therapeutic doses and did not potentiate the gastric damage induced by high doses of indomethacin. In vitro, the studied compounds (1-4) showed to be moderately active as scavengers of 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazil, 4 being the most active among them. Compound 4, on the contrary, was practically inactive on liposome peroxidation where compounds 1, 2, 3, which are modest anti-inflammatory agents, exerted a good or moderate effect.

Animals↗

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Effect of 2-methyltaurine and its enantiomers on arterial blood pressure.

Taurine has been shown to exert many biological effects. Among them, the ability of this amino acid to induce a reduction of arterial blood pressure, when administered intracerebroventricularly (i.c.v.) to mammals, has been established since a long time ago. To gain further information on the structure-activity requirements for taurine's hypotensive effect, the synthesis of 2-methyltaurine (2-aminopropanesulphonic acid) and the asymmetric synthesis of its enantiomers were performed; the enantiomeric purity of (R)- and (S)-2-methyltaurine was assayed by differential scanning calorimetry (DSC) and HPLC. The findings here reported show that the hypotensive effect elicited by the i.c.v. administration of racemate is mainly due to the (S)-enantiomer. The specificity of this effect was proved by the ability of the taurine antagonist TAG (6-aminomethyl-4H-3-methyl-1,2,4-benzothiadiazine 1,1-dioxide) to prevent it.

Animals↗

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Pregnancy related changes of opiate receptors identified in rat uterine membranes by 3H-naloxone binding.

3H-Naloxone was used to demonstrate the presence of specific opiate binding sites in uterine membrane preparations of rats. 3H-Naloxone binding (0.41-27 nM) was found to be rapid, saturable and reversible showing two populations of binding sites with the characteristic of high (KD 2.2 nM; Bmax 46.6 fmol/mg prot.) and low (KD 18.1 nM; Bmax 143.7 fmol/mg prot.) affinity. The number and affinity of the binding sites labelled by 3H-naloxone in the uterus were measured in the rat at mid (14 days), late (21 days) pregnancy and at parturition. The high and low affinity recognition sites labelled by 3H-naloxone showed a consistent reduction during pregnancy and at parturition without changes in the affinity constant. We concluded that pregnancy and parturition are associated with significant changes in the number of the opiate receptors bound in the uterus by 3H-naloxone. This phenomenon which seems to be linked with the several pregnancy-related changes in the levels of endogenous peptides and hormones could be relevant to further explain the pregnancy related changes in pain perception and maternal behavior.

Animals↗

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Alteration of opioid peptide and receptor ontogeny in the brain of pre- and postnatally low-level lead-exposed rats.

While the dopaminergic, the cholinergic and the GABAergic systems have been extensively studied in various models of lead intoxication, less attention has been devoted to the brain opiatergic system (opioid). We have recently reported that in rats pre- and postnatally exposed to a very low amount of lead (1 mg/kg/day) there was, at 40 days of age (behavioural anomalies such as hypermotility and decreased response to pain stimuli), an increased number of opiate receptors in the brain associated to a decrease of beta-endorphin and an increase of Met-enkephalin. The aim of the present study was to find out whether the above mentioned abnormalities of the opiatergic system (opioid) could be the result of a neurotoxic effect of lead exerted early in the development of the central nervous system of rats born from lead-poisoned parents. Here we report that the exposure to a low level of lead induces a decrease of beta-endorphin with a concomitant increase of opiate receptors measured at embryonic day 16 as well as at 7, 15, 40 and 60 days postnatally. On the other hand, an increased presence of Met-enkephalin was not detectable until postnatal day 7. Since endogenous opioid peptides, particularly beta-endorphin, have been recognized as important factors in central nervous system development, the described ability of lead to affect the ontogeny of the opiatergic system (opioid) might provide a new insight in understanding the complex mechanism of lead neurotoxicity.

Aging↗

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Evidence that exposure to methyl mercury during gestation induces behavioral and neurochemical changes in offspring of rats.

On day 15 of gestation, pregnant Sprague-Dawley rats were orally treated by gavage with 8 mg/kg of methyl mercury (MMC). At day 1 of postnatal life the levels of MMC in whole brain of exposed pups were found to be about 100 times higher than those of saline-exposed rats, while they were near to the control values at 21 days and practically normal at 60 days of age. Behavioral experiments showed that exposure to MMC in late gestation did not affect at any tested time (14, 21 and 60 days) locomotor activity or development of ultrasonic vocalization. An increased response to a challenge dose of amphetamine was, however, detected in MMC-exposed pups at day 14. This phenomenon was no longer evident at day 21 and 60 of age. In parallel, an increased density of dopamine receptors was found in the striatum at 14, but not at 21 and 60, days of age. From these data, we tentatively suggest that a high level of MMC induces a transient phenomenon of disuse-supersensitivity of the dopaminergic system. Moreover, further evidence that acute MMC exposure during prenatal life might induce permanent disturbances in learning and memory which could be partially related to a reduced functional activity of the glutamatergic system is provided.

Animals↗

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Increased brain concentrations of polyamines in rats with encephalopathy due to a galactosamine-induced fulminant hepatic failure.

Polyamine concentrations including putrescine, spermidine and spermine were documented in two brain areas of rats with mild and severe stages of hepatic encephalopathy (HE) due to fulminant hepatic failure induced by galactosamine HC1 injection (3 g kg-1 i.p.). In the mild stage of HE putrescine increased by 3-4 times whereas spermidine and spermine showed a slight increase. The scenario, however, was found to be changed going from the mild to the severe stage of HE, since in this last stage spermidine and spermine showed a further rise while putrescine was found to be significantly lower than in the mild stage of HE in both the brain areas studied. The changes in the ratio among the three polyamines with an enhanced prevalence in the severe stage of HE of spermidine and spermine are likely to be related to the exhaustion of the synthetic pathway of putrescine or to a reduction of the interconversion to this polyamine from spermidine and spermine. Considering that these last two polyamines potentiate the N-methyl-D-aspartate glutamate receptor mediated toxicity and that they might exert neurotoxic effects per se, there are clear reasons for suspecting an implication of the described changes of polyamines in the neurochemical mechanism which sustain HE and to surmise a potential therapeutic effect in this pathology of non-competitive antagonists of polyamine-site on N-methyl-D-aspartate glutamate receptors.

Animals↗

PubMedDate not supplied

Activity of single components of Ferula hermonis on male rat sexual behavior.

The influence of the single components of Ferula hermonis extract on sexual behavior was studied in male rats. Sexually potent and sluggish/impotent animals were orally treated acutely (2.5 mg/kg) and subchronically (0.25 mg/kg/day for 10 days) with ferutinin, teferdin and teferin. Ferutinin alone acutely administered in potent rats was able to reduce mount and intromission latencies, while in sluggish/impotent animals, it induced the same effects and additionally shortened the ejaculation latency, as teferdin did. Both substances increased testosterone levels in rats. Unlike teferdin, ferutinin subchronically administered in potent rats negatively affected appetitive and consummatory sexual behavior, reducing also testosterone serum levels. In conclusion, if repetitively administered, ferutinin was able to stimulate sexual behavior after acute ingestion, but exerted a negative influence on the sexual capacity of potent male rats, whereas teferdin only improved copulatory performance of sluggish/impotent animals.

Animals↗