68 research outputs found
Lymphocyte DNA damage in rats exposed to pyrethroids: effect of supplementation with Vitamins E and C.
Pesticides have been considered potential chemical mutagens. In fact, some studies show that various agrochemical ingredients possess mutagenic properties inducing mutations, chromosomal alterations or DNA damage. Experimental evidence shows a marked correlation between mutagenicity and carcinogenicity and indicates that short-term mutagenicity tests are useful for
predicting carcinogenicity. The present study on rat exposed to two pyrethroids, cypermethrin and permethrin, showed different lymphocyte DNA damage depending on the type of pyrethroid, the dose, and the period of treatment. Data obtained from comet assay showed that oral treatment with 150 mg/kg body weight/day of permethrin (corresponding to 1/10 of LD50) for 60 days, induced a significant increase in all comet parameters. No lymphocyte DNA damage was measured after treatment with 25 mg/kg body weight/day of cypermethrin (corresponding to 1/10 of LD50) for the same period. A higher dose of permethrin (300 mg/kg body weight/day), for a shorter period (22 days), did not induce lymphocyte DNA damage, while supplementation with 200 mg/kg of Vitamins E and C protected erythrocytes against plasma membrane lipids peroxidation. Moreover, treatment with Vitamins E and C maintained the activity of glutathione peroxidase, which was reduced in the presence of permethrin, and reduced the osmotic fragility, which had increased following permethrin treatment
Intergenerational effect of early life exposure to permethrin: changes in global DNA methylation and in Nurr1 gene expression
Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM), a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. Through gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Thirty-three percent of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Further studies are however needed to elucidate the molecular mechanisms, but, despite this, an intergenerational PERM-induced damage on progenies has been identified for the first time
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
Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids
Pyrethroids are a class of insecticides involved in different neurological disorders. They cross the blood–brain barrier and exert
their effect on dopaminergic system, contributing to the burden of oxidative stress in Parkinson’s disease through several pathways.
The aim of the present study was to evaluate the effect of neonatal exposition to permethrin and cypermethrin (1/10 of DL50) in rats
from the eighth to the fifteenth day of life. Open-field studies showed increased spontaneous locomotor activity in the groups treated
with permethrin and the one treated with cypermethrin, while a higher number of center entries and time spent in the center was
observed for the cypermethrin-treated group. Lower dopamine and higher homovanillic acid levels were measured in the striatum
from both treated groups. A reduction of blood glutathione peroxidase content was measured, while no change in blood superoxide
dismutase was observed. Carbonyl group formation increased in striatum, but not in erythrocytes. Lipid peroxidation occurred in
erythrocytes, but not in striatum. No changes in fluidity at different depths of plasma membrane were measured in striatum or
erythrocytes. The activation of monocyte NADPH oxidase by phorbol esters (PMA) shows that superoxide anion production was
reduced in the pyrethroid-treated groups compared to the control group. Our studies suggest that neonatal exposition to permethrin or
cypermethrin induces long-lasting effects after developmental exposure giving changes in open-field behaviors, striatal monoamine
level, and increased oxidative stress. Although the action of pyrethroids on various target cells is different, a preferential interaction
with the extracellular side of plasma membrane proteins can be observed
Hair Microelement Profile as a Prognostic Tool in Parkinson’s Disease
Abstract: Changes in the homeostasis of metals and microelements have been demonstrated in
Parkinson’s disease, whose etiology includes both a genetic and environmental basis. We studied
the difference of microelements in the hair of Parkinson’s disease subjects (n = 46) compared with
healthy controls (n = 24). Hair was chosen as a representative matrix to measure microelements, since
it is a vehicle of substance excretion from the human body and it allows for long-term evaluation
of metal exposure. An inductively coupled plasma mass spectrometry (ICP-MS) analysis of hair
collected from 24 Parkinson’s patients compared with their healthy relatives used as controls shows a
significant decrease in Ca (U = 166, p = 0.012),), Mg (U = 187, p = 0.037), and Sr (U = 183, p = 0.030).
Cd and Ca/Mg were decreased, and Cu was increased, in patients with respect to their healthy
related controls at the limit of significance (p = 0.0501). Principal Component Analysis (PCA) of
these microelements in hair shows a clustering into two groups according to gender, disease severity
according to the Hoehn–Yahr scale, and pharmacological therapy. This pilot study represents a
starting point for future investigations where a larger group of subjects will be involved to define
other microelements useful when screening for early biomarkers of Parkinson’s disease
Changes on fecal microbiota in rats exposed to permethrin during postnatal development
Alteration of the gut microbiota through diet and environmental contaminants may disturb the mammalian digestive system, leading to various diseases. Because most exposure to environmentally pyrethroid pesticides such as permethrin (PERM) occurs through the diet, the commensal gut microbiota is likely to be exposed to PERM. The study aimed at evaluating the effect of low-dose exposure to PERM in early life on the composition of fecal microbiota in rats. Over a 4-month follow-up period, fecal microbiota and short-chain fatty acids were measured in order to identify possible differences between PERM-treated rats and controls. Further in vitro antimicrobial experiments were conducted to establish the antibacterial activity of PERM against different strains to obtain Minimal Inhibitory Concentrations. The main finding focused on the reduced abundance of Bacteroides-Prevotella-Porphyromonas species, increased Enterobacteriaceae and Lactobacillus in PERM-treated rats compared to controls. Changes of acetic and propionic acid levels were registered in PERM-treated group. From in vitro studies, PERM showed higher antibacterial activity against beneficial bacteria such as Bifidobacterium and Lactobacillus paracasei, while to inhibit potential pathogens as Staphylococcus aureus and Escherichia coli PERM concentration needed to be increased. In summary, exposure to PERM could affect the fecal microbiota and could be a crucial factor contributing to the development of diseases
The impact of early life permethrin exposure on development of neurodegeneration in adulthood.
Early life environmental exposure to pesticides could play a critical role in the onset of age-related diseases.
The present study aims to evaluate in brain, plasma and leukocytes of 300 day-old rats, the effect of a low dose of the insecticide permethrin administered during early life (1/50 LD50, from 6th to 21st day of life).
The outcomes show that Nurr1, mRNA and protein expression, as well as calcium and NO levels are decreased in striatum. Moreover, the pesticide induces an imbalance in glutamate, calcium and NO in hippocampus. Low calcium concentrations in leukocytes and in plasma were observed, while increased NO and decreased SOD plasma levels were measured.
The results suggest that permethrin intake at a dose close to the NOAEL (25 mg/kg) during the perinatal period can interact with Nurr1 by reducing its expression on striatum nucleus. Consequently, the maintenance of dopaminergic neurons as well as Nurr1 inhibitory effect on the production of proinflammatory mediators fails.
The changes in biological markers found in our animal model could represent the basis to study neurodegenerative diseases whose development depends on individual gene signature and life style
Synthesis and study of L-dopa-glutathione codrugs as new anti-Parkinson agents with free radical scavenging properties
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
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