Early life permethrin exposure leads to hypervitaminosis D, nitric oxide and catecholamines impairment

Mirto

et al. 2015

Self Cite

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.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression

Bordoni

Mirto

et al. 2015

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“…, idiopathic Parkinson’s disease (PD)) and early onset of the disease has been observed in exposed occupational subjects with no family history of disease among their first-degree relatives [ 3 ]. At the same time, epidemiological investigations and studies in laboratory animals have shown evidence of the role of metals, neurotoxicants and pesticides in the onset of PD [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Taking into account this evidence, the aim of this study was to evaluate the level of metals and microelements in neck hair from permethrin (PERM)-treated rats exposed to the pesticide during early life. Two time points were chosen for assessment in rats, at six and 12 months of age, because at this age, animals showed dopamine, Nurr1, oxidative stress and behavioral abnormalities similar to those observed in Parkinson’s-like diseases [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Data were discussed considering the role of trace elements and the biomarkers previously measured in this animal model of neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Metal and Microelement Biomarkers of Neurodegeneration in Early Life Permethrin-Treated Rats

Ferraro

Giovannetti

et al. 2016

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Abstract:Hair is a non-invasive biological material useful in the biomonitoring of trace elements because it is a vehicle for substance excretion from the body, and it permits evaluating long-term metal exposure. Here, hair from an animal model of neurodegeneration, induced by early life permethrin treatment from the sixth to 21th day of life, has been analyzed with the aim to assess if metal and microelement content could be used as biomarkers. A hair trace element assay was performed by the ICP-MS technique in six-and 12-month-old rats. A significant increase of As, Mg, S and Zn was measured in the permethrin-treated group at 12 months compared to six months, while Si and Cu/Zn were decreased. K, Cu/Zn and S were increased in the treated group compared to age-matched controls at six and 12 months, respectively. Cr significantly decreased in the treated group at 12 months. PCA analysis showed both a best difference between treated and age-matched control groups at six months. The present findings support the evidence that the Cu/Zn ratio and K, measured at six months, are the best biomarkers for neurodegeneration. This study supports the use of hair analysis to identify biomarkers of neurodegeneration induced by early life permethrin pesticide exposure.

“…Furthermore, a correlation between idiopathic PD and early onset of the disease has been observed not only in genetic forms but also in exposed occupational subjects with no family history of the disease among their first-degree relatives, highlighting the key role of environmental factors in the development of Parkinson’s disease [ 2 ]. At the same time, epidemiological investigations on humans and studies on animal models of Parkinson’s-like diseases have shown that metals, neurotoxicants, and pesticides play a key role in the onset of PD [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Metals can accumulate in microscopic proteinopathies leading simultaneously to their decrease in cellular microenvironments, where they play a key role in biological processes [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Hair Microelement Profile as a Prognostic Tool in Parkinson’s Disease

Ferraro

Piangerelli

et al. 2016

Changes in the homeostasis of metals and microelements have been demonstrated inParkinson'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.