Early life permethrin treatment leads to long-term cardiotoxicity

Vadhana, M.S. Dhivya; Arumugam, Somasundaram; Carloni, Manuel; Nasuti, Cinzia; Gabbianelli, Rosita

doi:10.1016/j.chemosphere.2013.05.073

Cited by 40 publications

(27 citation statements)

References 44 publications

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“…As shown in Figure 1c, mRNA content of Gclc, Gclm, and Gst2a exhibited age-dependent declines of 19.6%, 31.4%, and 40%, respectively. Because Nrf2 mRNA levels vary in tissues [17] and in response to certain toxicological stressors [18–20], we sought to determine whether lowered Nrf2 transcript levels may be responsible for the age-related loss of Nrf2 protein content. On the contrary, hepatic Nrf2 mRNA values exhibited no significant age-dependent changes (Figure 1c; p>0.14), indicating that dysregulation of Nrf2 transcription with age does not account for attenuation of Nrf2 protein levels.…”

Section: Resultsmentioning

confidence: 99%

Age-related loss of hepatic Nrf2 protein homeostasis: Potential role for heightened expression of miR-146a

Smith

Shay

Thomas

et al. 2015

Free Radical Biology and Medicine

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Summary Nrf2 regulates the expression of numerous anti-oxidant, anti-inflammatory, and metabolic genes. We observed that, paradoxically, Nrf2 protein levels decline in the livers of aged rats despite the inflammatory environment evident in that organ. To examine the cause(s) of this loss, we investigated the age-related changes in Nrf2 protein homeostasis and activation in cultured hepatocytes from young (4-6 months) and old (24-28 months) Fischer 344 rats. While no age-dependent change in Nrf2 mRNA levels was observed (p>0.05), Nrf2 protein content, and the basal and anetholetrithione (A3T)-induced expression of Nrf2-dependent genes were attenuated with age. Conversely, overexpression of Nrf2 in cells from old animals reinstated gene induction. Treatment with A3T, along with bortezomib to inhibit degradation of existing protein, caused Nrf2 to accumulate significantly in cells from young animals (p<0.05), but not old, indicating a lack of new Nrf2 synthesis. We hypothesized that the loss of Nrf2 protein synthesis with age may partly stem from an age-related increase in microRNA inhibition of Nrf2 translation. Microarray analysis revealed that six microRNAs significantly increase >2-fold with age (p<0.05). One of these, miRNA-146a, is predicted to bind Nrf2 mRNA. Transfection of hepatocytes from young rats with a miRNA-146a mimic caused a 55% attenuation of Nrf2 translation that paralleled the age-related loss of Nrf2. Overall, these results provide novel insights for the age-related decline in Nrf2 and identify new targets to maintain Nrf2-dependent detoxification with age.

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Section: Resultsmentioning

confidence: 99%

Age-related loss of hepatic Nrf2 protein homeostasis: Potential role for heightened expression of miR-146a

Smith

Shay

Thomas

et al. 2015

Free Radical Biology and Medicine

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“…It is believed that the cardiovascular system is susceptible to external factors during pregnancy and after birth. Studies suggest that chronic use of permethrin at a dose of 1/50 LD50 leads to oxidative stress and damages heart cells [ 35 , 36 ]. The effect of early treatment with permethrin on the development of cardiac toxicity in 500-day-old rats was studied [ 36 ].…”

Section: Permethrinmentioning

confidence: 99%

“…Studies suggest that chronic use of permethrin at a dose of 1/50 LD50 leads to oxidative stress and damages heart cells [ 35 , 36 ]. The effect of early treatment with permethrin on the development of cardiac toxicity in 500-day-old rats was studied [ 36 ]. The expression of nuclear factor erythroid 2–related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) genes, calcium levels, heart surface area and glyceraldehyde 3-phosphate dehydrogenase (EC.…”

Section: Permethrinmentioning

confidence: 99%

“…In summary, exposure to orally administrated low-dose pesticides at an early stage of life, from 6 to 21 days, may have long-term consequences, such as cardiac hypertension, elevated calcium levels, and the expression of the Nrf-2 gene at an elderly age [ 36 ]. In the same study, decreased plasma membrane fluidity, an increase in plasma cholesterol, interleukin 1 (IL-1), 2 (IL-2), 10 (IL-10) and interferon γ (IFN-γ), and a decrease in plasma albumin concentration were observed [ 36 ]. Lowered cholesterol levels, decreased reduced glutathione (GSH) levels and increased glutathione peroxidase (EC 1.11.9.1, GPx) activity in heart mitochondria were detected.…”

Section: Permethrinmentioning

confidence: 99%

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Current Research on the Safety of Pyrethroids Used as Insecticides

et al. 2018

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Pyrethroids are synthetic derivatives of natural pyrethrins extracted from Chrysanthemum cinerariaefolium. They are 2250 times more toxic to insects than to vertebrates due to insects’ smaller size, lower body temperature and more sensitive sodium channels. In particular, three pyrethroid compounds, namely deltamethrin, permethrin, and alpha-cypermethrin, are commonly used as insecticides and are recommended for in-home insect control because they are considered to be relatively non-toxic to humans in all stages of life. However, recent data show that they are not completely harmless to human health as they may enter the body through skin contact, by inhalation and food or water, and absorption level depending on the type of food. Permethrin seems to have an adverse effect on fertility, the immune system, cardiovascular and hepatic metabolism as well as enzymatic activity. Deltamethrin induces inflammation, nephro- and hepatotoxicity and influences the activity of antioxidant enzymes in tissues. Alpha-cypermethrin may impair immunity and act to increase glucose and lipid levels in blood. The aim of the review is to provide comprehensive information on potential hazards associated to human exposure to deltamethrin, permethrin and alpha-cypermethrin. The results of presented studies prove that the insecticides must be used with great caution.

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“…However, recent publications have suggested that there may be significant aspects that were not considered in the original evaluation of pyrethroid toxicity. For example in neurodevelopmental studies, repeated exposure to pyrethroids at dosage close to the NOAEL that do not produce frank poisoning or signs of obvious abnormalities (for example, body weight loss, red eyes, etcetera ) in neonates may cause long lasting effects in adult age [9-15]. In previous studies, we exposed neonatal rats to PERM during the developmental period until weaning at 21 days, at a dose of 34 mg/kg, close to the NOAEL.…”

Section: Introductionmentioning

confidence: 99%

Neonatal exposure to permethrin pesticide causes lifelong fear and spatial learning deficits and alters hippocampal morphology of synapses

Nasuti

Fattoretti

Carloni

et al. 2014

J Neurodevelop Disord

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BackgroundDuring 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.MethodsNeonatal 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.ResultsIn 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.ConclusionsEarly-life permethrin exposure imparts long-lasting consequences on the hippocampus such as impairment of long-term memory storage and synaptic morphology.

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Early life permethrin treatment leads to long-term cardiotoxicity

Cited by 40 publications

References 44 publications

Age-related loss of hepatic Nrf2 protein homeostasis: Potential role for heightened expression of miR-146a

Age-related loss of hepatic Nrf2 protein homeostasis: Potential role for heightened expression of miR-146a

Current Research on the Safety of Pyrethroids Used as Insecticides

Neonatal exposure to permethrin pesticide causes lifelong fear and spatial learning deficits and alters hippocampal morphology of synapses

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