170 research outputs found
Effect of permethrin plus antioxidants on locomotor activity and striatum in adolescent rats
Pyrethroids are important insecticides used largely because of their high activity as an insecticide and
their low mammalian toxicity. Some studies have demonstrated that these products show neurotoxic
effects on the mammalian central nervous system.
The aim of the present study was to investigate the propensity of permethrin to induce oxidative stress
in adolescent rats and its possible attenuation by Vitamin E alone or + Coenzyme Q10. Data indicated
that adolescent rats exposed to permethrin exhibited alteration in the locomotor activity and plasma
membrane fluidity of striatum. Vitamin E +Q10 and Vitamin E alone supplementation reversed the negative
effect on central nervous system. Permethrin alteration of striatum plasma membrane fluidity was
restored by Vitamin E +Q10. Data obtained from red blood cells showed that permethrin did not induce
any modification of plasma membrane fluidity in adolescent rats, whereas antioxidants supplementation
induced pro-oxidant effect.
In summary some differences between antioxidant treatments were observed at striatum level: Coenzyme
Q10 + Vitamin E maintains plasma membrane fluidity, while Vitamin E is more effective to preserve
GSH level
L-dopa and dopamine-(R)-alpha-lipoic acid conjugates as multifunctional codrugs with antioxidant properties
A series of multifunctional codrugs (1-4), obtained by joining L-Dopa (LD) and dopamine (DA) with
(R)-R-lipoic acid (LA), was synthesized and evaluated as potential codrugs with antioxidant and iron-chelating
properties. These multifunctional molecules were synthesized to overcome the pro-oxidant effect associated
with LD therapy. The physicochemical properties, together with the chemical and enzymatic stabilities of
synthesized compounds, were evaluated in order to determine both their stability in aqueous medium and
their sensitivity in undergoing enzymatic cleavage by rat and human plasma to regenerate the original drugs.
The new compounds were tested for their radical scavenging activities, using a test involving the Fe (II)-
H2O2-induced degradation of deoxyribose, and to evaluate peripheral markers of oxidative stress such as
plasmatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the plasma.
Furthermore, we showed the central effects of compounds 1 and 2 on spontaneous locomotor activity of
rats in comparison with LD-treated animals. From the results obtained, compounds 1-4 appeared stable at
a pH of 1.3 and in 7.4 buffered solution; in 80% human plasma they were turned into DA and LD. Codrugs
1-4 possess good lipophilicity (log P > 2 for all tested compounds). Compounds 1 and 2 seem to protect
partially against the oxidative stress deriving from auto-oxidation and MAO-mediated metabolism of DA.
This evidence, together with the “in vivo” dopaminergic activity and a sustained release of the parent drug
in human plasma, allowed us to point out the potential advantages of using 1 and 2 rather than LD in
treating pathologies such as Parkinson’s disease, characterized by an evident decrease of DA concentration
in the brain
Codrugs linking L-Dopa and sulfur-containing antioxidants: new pharmacological tools against Parkinson’s Disease
A series of multifunctional codrugs (1-6) were synthesized to overcome the pro-oxidant effect associated with L-dopa (LD) therapy. Target compounds release LD and dopamine (DA) in human plasma after enzymatic hydrolysis, displaying an antioxidant effect superior to that of N-acetylcysteine (NAC). After intracerebroventricular injection of codrug 4, the levels of DA in the striatum were higher than those in LD-treated groups, indicating that this compound has a longer half-life in brain than LD
A singular case of Graves' disease in congenital thyroid hemiagenesis
We report the observation of an unusual case of Graves' disease associated with thyroid hemiagenesis. A 41-year-old woman who presented with symptoms and clinical signs of hyperthyroidism was discovered to have thyroid hemiagenesia of the left lobe. Thyroid ultrasound scan showed enlargement of the right lobe with a single nodule, and absence of the left lobe; isotope scan showed homogeneous uptake in the single lobe and nodule. Ophthalmopathy, which was absent at presentation, developed after two years; after a further 2 years the patient developed decompensated hypothyroidism requiring thyroxine replacement. This is the first case of Graves' disease in thyroid hemiagenesis evolved to hypothyroidism, and a rare case of thyroid ophthalmopathy accompanying this condition
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