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Effect of choline-containing phospholipids on brain cholinergic transporters in the rat.
No full textpPKCepsilon mediated metalloproteinase 2 and 9 levels upon ibuprofen and lipoic acid coniugate (codrug 1) treatment in an Alzheimer disease rat brain model
No full textNew pharmacologic tools against Parkinson's disease: L-Dopa-antioxidant codrugs containing the methionine residue
No full textEffect of 17b-estradiol on striatal dopaminergic transmission induced by permethrin in early childhood rats
No full textA positive effect of estrogen treatment has been observed in neurodegenerative diseases such as
Parkinson’s disease. Since 17b-estradiol can modulate positively dopaminergic system, here we sought
to evaluate the effect of 17b-estradiol supplementation on an animal model developing dopaminergic
alterations on nucleus of striatum after neonatal exposure to permethrin pesticide. The goal of the study
was to verify if the co-treatment with 17b-estradiol could protect against the damage induced by
pesticide exposure in early life.
Permethrin treated rats showed a decrease of dopamine and Nurr1 gene expression in striatum, while a
more pronounced decrease of dopamine was observed in rats co-administered with permethrin + 17bestradiol.
No difference between control and permethrin treated rats was observed in both mRNA of ERa
and ERb, whereas the rats co-administered with permethrin + 17b-estradiol showed a down-regulation
of ERa expression. The in vitro studies showed that permethrin, at high concentration may have an
antagonist effect on ERa and even more pronounced in ERb, thus suggesting that permethrin may block
the estrogen neuroprotective effects.
In conclusion, in male rats, the administration of estrogen further enhanced the impairment of dopaminergic
transmission due to exposure to permethrin
Ibuprofen and lipoic acid diamide as co-drugs with neuroprotective activity: pharmacological properties and effects in β-amyloid (1-40) infused Alzheimer’s disease rat model.
No full textEffects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats.
Full text linkPesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12h after the last treatment was 41.50μg/L and it was completely eliminated after 96h
synthesis and Activity of L-Dopa-Thiol antioxidant Co-drugs and New anti-PArkinson Agents with free Radical Scavenging Properties
No full textsynthesis and biological evaluation as anti-Parkinson agent of an analogue of Glutathione-L-Dopa containing methionine in place of the cysteinil residue
No full textCNS delivery of L-Dopa by a new Hybrid Glutathione-Methionine peptidomimetic prodrug
No full textParkinson’s disease (PD) is a neurodegenerative disorder associated primarily with loss of dopamine (DA) neurons in the nigrostriatal system. With the aim of increasing the bioavailability of L-dopa (LD) after oral administration and of overcoming the pro-oxidant effect associated with LD therapy, we designed a peptidomimetic LD prodrug (1) able to release the active agent by enzyme catalyzed hydrolysis. The physicochemical properties, as well as the chemical and enzymatic stabilities of the new
compound, were evaluated in order to check both its stability
in aqueous medium and its sensitivity towards enzymatic cleavage, providing the parent LD drug, in rat and human plasma. The radical scavenging activities of prodrug 1 was tested by using both the DPPH–HPLC and the DMSO competition methods. The results indicate that the replacement of cysteine GSH portion by methionine confers resistance to oxidative degradation in gastric fluid.
Prodrug 1 demonstrated to induce sustained delivery of DA
in rat striatal tissue with respect to equimolar LD dosages.
These results are of significance for prospective therapeutic
application of prodrug 1 in pathological events associated
with free radical damage and decreasing DA concentration
in the brain
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