104 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
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
Neonatal exposure to permethrin pesticide causes lifelong fear and spatial learning deficits and alters hippocampal morphology of synapses.
During the neurodevelopmental period, the brain is potentially more susceptible to environmental exposure to pollutants. The aim was to determine if neonatal exposure to permethrin (PERM) pesticide, at a low dosage that does not produce signs of obvious abnormalities, could represent a risk for the onset of diseases later in the life.
METHODS:
Neonatal rats (from postnatal day 6 to 21) were treated daily by gavage with a dose of PERM (34 mg/kg) close to the no-observed-adverse-effect level (NOAEL), and hippocampal morphology and function of synapses were investigated in adulthood. Fear conditioning, passive avoidance and Morris water maze tests were used to assess cognitive skills in rats, whereas electron microscopy analysis was used to investigate hippocampal morphological changes that occurred in adults.
RESULTS:
In both contextual and tone fear conditioning tests, PERM-treated rats showed a decreased freezing. In the passive avoidance test, the consolidation of the inhibitory avoidance was time-limited: the memory was not impaired for the first 24 h, whereas the information was not retained 72 h following training. The same trend was observed in the spatial reference memories acquired by Morris water maze. In PERM-treated rats, electron microscopy analysis revealed a decrease of synapses and surface densities in the stratum moleculare of CA1, in the inner molecular layer of the dentate gyrus and in the mossy fibers of the hippocampal areas together with a decrease of perforated synapses in the stratum moleculare of CA1 and in the inner molecular layer of the dentate gyrus.
CONCLUSIONS:
Early-life permethrin exposure imparts long-lasting consequences on the hippocampus such as impairment of long-term memory storage and synaptic morphology
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
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
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
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
Dopaminergic system is differently altered in hippocampus and facial nucleus of trimethyltin rat model
Trimethyltin (TMT) is an organotin compound which is considered a useful tool to obtain an animal model of neurodegeneration associated with cognitive impairment (Pompili et al., 2011; Geloso et al., 2011). In the present work, this model was used in order to investigate the animal behaviour in association with the immunohistochemical expression of dopaminergic system (D1- and D2-like receptors and dopamine transporters DAT, VMAT-1 and -2) and cells viability (NEU-N) in the rat hippocampus and facial nucleus regions. TMT-treated group showed impaired spatial reference memory in a Morris water maze task compared to control group whereas the memory consolidation tested 24h after was preserved. In the open field, TMT-treated rats showed a decreased in time spent in rearing episodes reflecting a lower interest to explore a novel environment. In the hippocampal area of TMT-treated group, cell viability was significantly reduced by 45.9% whereas the D1, D2, DAT and VMAT- 2 receptor proteins immunoreactivity was significantly decreased by 57.5, 72.8, 64.1, 72.1%. In the facial nucleus, immunoreactivity reduction was observed only for dopamine transporters (average: 60% about) while the NEU-N reduction was 40%. These data were confirmed by real time RT-PCR analysis. These results suggest a differential involvement of the D1-type and D2-type receptors in the regulation of learning and memory. Besides, alterations on the functional ratio of DAT to VMAT-2 could predispose the cells to injury even at very low doses of TMT. The data obtained in facial nucleus demonstrate a different sensibility to xenobiotic of dopamine receptors and transporters. The TMT model could contribute to elucidate the role of dopaminergic system on two different CNS regions. Supported by PRIN 2008 - prot. 20089MANHH_002 and prot. 20089MANHH_003
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