Permethrin Research Articles

Exposure to Sub-Lethal Doses of Permethrin Is Associated with Neurotoxicity: Changes in Bioenergetics, Redox Markers, Neuroinflammation and Morphology.

Permethrin (PERM) is a member of the class I family of synthetic pyrethroids. Human use has shown that it affects different systems, with wide health dysfunctions. Our aim was to determine bioenergetics, neuroinflammation and morphology changes, as redox markers after subacute exposure to PERM in rats. We used MDA determination, protein carbonyl assay, mitochondrial O2 consumption, expression of pro-inflammatory cytokines and a deep histopathological analysis of the hippocampus. PERM (150 mg/kg and 300 mg/kg body weight/day, o.v.) increased lipoperoxidation and carbonylated proteins in a dose-dependent manner in the brain regions. The activities of antioxidant enzymes glutathione peroxidase, reductase, S-transferase, catalase, and superoxide dismutase showed an increase in all the different brain areas, with dose-dependent effects in the cerebellum. Cytokine profiles (IL-1β, IL-6 and TNF-α) increased in a dose-dependent manner in different brain tissues. Exposure to 150 mg/kg of permethrin induced degenerated and/or dead neurons in the rat hippocampus and induced mitochondrial uncoupling and reduction of oxidative phosphorylation and significantly decreased the respiratory parameters state 3-associated respiration in complex I and II. PERM exposure at low doses induces reactive oxygen species production and imbalance in the enzymatic antioxidant system, increases gene expression of pro-inflammatory interleukins, and could lead to cell damage mediated by mitochondrial functional impairment.

Restorative potential of (\u2212)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue

We examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

Ozonolysis of Permethrin in the Atmosphere: Mechanism, Kinetics, and Evaluation of Toxicity.

Pyrethroid, a pesticide widely used worldwide, could mimic, block, or synergize the effects of endogenous hormones in humans or mammals after entering into the atmosphere and after being sprayed and applied in large quantities. This research aims to study the mechanism, kinetics, and eco-toxicity evaluation of the ozonolysis of permethrin (PER)-one of the typical pyrethroid (type I) pesticides. Existing experimental studies only predicted that ozonolysis of PER could generate a cycloperoxy analogue of PER (IM13-1-11), and the reaction mechanism has not yet been completed. To make up for the lack of experimental results, the 13 primary reaction pathways of PER and ozone, as well as the subsequent reactions of Criegee intermediates with small molecules such as NOx, COx, SO2, and O2, have been studied to propose new reaction paths by quantum chemical calculations in this work. We calculated the total reaction rate constant of PER and ozone at 298 K and 1 atm based on the calculated thermodynamic data and the transition state theory (TST), which was compared with the experimental values to prove the reliability of our results. Based on the quantitative structure and activity relationship, we predicted the acute and chronic toxicity of PER and its products of ozonolysis to three representative organisms-fish, daphnia, and green algae to avoid animal experiments. The results show that ozonolysis products of PER are still extremely harmful to the environment and should be taken seriously, although the products have less toxicity than PER.

High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats

This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Cardiac content of peroxidation malonaldehyde, protein carbonyls, and reactive oxygen species were remarkably elevated, while glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities were inhibited in animals receiving a HFD and/or PER. Furthermore, cardiac DNA fragmentation and upregulation of Bax and caspase-3 gene expression supported the ability of HFD and/or PER to induce apoptosis and inflammation in rat hearts. High cardiac TGF-β1 expression explained the profibrotic effects of PER either with the standard diet or HFD. Masson’s Trichrome staining clearly demonstrated that HFD and PER could cause cardiac fibrosis. Additionally, increased oxidized LDL and the presence of several lipid droplets in arterial tissues highlighted the atherogenic effects of HFD and/or PER in rats. Such PER-induced cardiac and vascular dysfunctions were aggravated by and associated with a HFD, implying that obese individuals may be more vulnerable to PER exposure. Collectively, post-weaning exposure to HFD and/or PER may promote heart failure and fibrosis, demonstrating the pleiotropic effects of exposure to environmental factors early in life.

Lacto-N-fucopentaose-III (LNFPIII) ameliorates acute aberrations in hippocampal synaptic transmission in a Gulf War Illness animal model

Approximately one-third of Persian Gulf War veterans are afflicted by Gulf War Illness (GWI), a chronic multisymptom condition that fundamentally presents with cognitive deficits (i.e., learning and memory impairments) and neuroimmune dysfunction (i.e., inflammation). Factors associated with GWI include overexposures to neurotoxic pesticides and nerve agent prophylactics such as permethrin (PM) and pyridostigmine bromide (PB), respectively. GWI-related neurological impairments associated with PB-PM overexposures have been recapitulated in animal models; however, there is a paucity of studies assessing PB-PM-related aberrations in hippocampal synaptic plasticity and transmission that may underlie behavioral impairments. Importantly, FDA-approved neuroactive treatments are currently unavailable for GWI. In the present study, we assessed the efficacy of an immunomodulatory therapeutic, lacto-N-fucopentaose-III (LNFPIII), on ameliorating acute effects of in vivo PB-PM exposure on synaptic plasticity and transmission as well as trophic factor/cytokine expression along the hippocampal dorsoventral axis. PB-PM exposure resulted in hippocampal synaptic transmission deficits 48 h post-exposure, a response that was ameliorated by LNFPIII coadministration, particularly in the dorsal hippocampus (dH). LNFPIII coadministration also enhanced synaptic transmission in the dH and the ventral hippocampus (vH). Notably, LNFPIII coadministration elevated long-term potentiation in the dH. Further, PB-PM exposure and LNFPIII coadministration uniquely altered key inflammatory cytokine and trophic factor production in the dH and the vH. Collectively, these findings demonstrate that PB-PM exposure impaired hippocampal synaptic responses 48 h post-exposure, impairments that differentially manifested along the dorsoventral axis. Importantly, LNFPIII ameliorated GWI-related electrophysiological deficits, a beneficial effect indicating the potential efficacy of LNFPIII for treating GWI.

Gulf War Agent Exposure Causes Dose‐Dependent Impairment of Memory Formation and Exercise Intolerance in a Mouse Model of Gulf War Illness

Gulf War Illness (GWI) is a chronic multi-symptom condition that still affects a third of veterans who served in the 1991 Persian Gulf War (GW). Latently-emerging and persistent symptoms fall into 5 general domains: neurological/cognition/mood, muscle/joint pain, respiratory, gastrointestinal disturbances and especially chronic fatigue. In particular, veterans exhibit CNS deficits in the neuropsychological domains of visuospatial abilities, attention/executive functioning, and learning/memory. GWI remains untreated due its poorly understood etiology and pathophysiology. It is suggested that GWI is a result of continuous exposure of military personnel to GW agents (pyridostigmine bromide, (PB), permethrin (PER), diethyltoluamide (DEET) and deployment/combat stress. To further investigate the cognitive manifestations of GWI pathophysiology, we studied the effects of chronic GW agent exposure in adult C57Bl/6N males utilizing a repeated measures design. The dosing paradigm consisted of 5 d/week for 28d of exposure to two doses of PB (6.5 mg/kg/d, 2x/d and 8.7 mg/kg/d, 1x/d; po), PER (1.3 mg/kg/d; top) in 70% ETOH, DEET (1650 mg/kg/d in DMSO) and stress 5 min/d (n=5–7/group). Two controls were included: sham (saline po, 70% ETOH and DMSO top) and sham/stress. Behavioral endpoints were measured at different timepoints post treatment (PT) up to PT160d. The 8.7 mg/kg/d dose was more effective in modeling cognitive deficits on the passive avoidance test since this group failed to avoid the aversive dark chamber at the 24h, and 7d and/or 3d retention timepoints at PT70. A repeat test at PT120 indicated that the 8.7 and sham/stress (P<.01) but not the 6.5 mg/kg/d group displayed retention of emotional reactivity memory at all test timepoints. In the novel object recognition test, performed at PT17, GW groupsbut not sham/stress displayed deficient memory retention at 24h (P<.01). On the Barnes Maze, no GW exposure effects on reference memory were noted during acquisition training nor a 24h acquisition probe trial. Since the neuropsychological deficits seen in GW chemical exposures can be exacerbated by comorbid mood-related conditions, animals were tested for anxiety and depression but no GW-specific effects were found. To model chronic fatigue, using a 5-day exercise endurance test we found that 8.7 mg/kg/d showed decreased latency to exhaustion at PT23 and PT161 compared to sham/stress (P<.05, P<.01). This effect could not be attributed to problems with motor coordination as measured on Suok and rotarod tests. In summary, the GW agent exposure paradigm produces specific cognitive deficits in associative aversive learning and novel object recognition memory but not visuospatial (reference) memory. GW agents also cause mice to tire faster during exercise without deficits in motor coordination. This animal model may be useful in examining common mechanisms underlying deficient cognitive performance and chronic fatigue in GWI.

Investigation of steatosis profiles induced by pesticides using liver organ-on-chip model and omics analysis

Several studies have reported a correlation between pesticides exposure and metabolic disorders. Dichlorodiphenyltrichloroethane (DDT) and permethrin (PMT), two pesticides highly prevalent in the environment, have been associated to dysregulation of liver lipids and glucose metabolisms and non-alcoholic fatty liver disease (NAFLD). However, the effects of DDT/PMT mixtures and mechanisms mediating their action remain unclear. Here, we used multi-omic to investigate the liver damage induced by DDT, PMT and their mixture in rat liver organ-on-chip. Organ-on-chip allow the reproduction of in vivo-like micro-environment. Two concentrations, 15 and 150 μM, were used to expose the hepatocytes for 24 h under perfusion. The transcriptome and metabolome analysis suggested a dose-dependent effect for all conditions, with a profile close to control for pesticides low-doses. The comparison between control and high-doses detected 266/24, 256/24 and 1349/30 genes/metabolites differentially expressed for DDT150, PMT150 and Mix150 (DDT150/PMT150). Transcriptome modulation reflected liver inflammation, steatosis, necrosis, PPAR signaling and fatty acid metabolism. The metabolome analysis highlighted common signature of three treatments including lipid and carbohydrates production, and a decrease in amino acids and krebs cycle intermediates. Our study illustrates the potential of organ-on-chip coupled to multi-omics for toxicological studies and provides new tools for chemical risk assessment.

Effects of Permethrin or Deltamethrin Exposure in Adult Sprague Dawley Rats on Acoustic and Light Prepulse Inhibition of Acoustic or Tactile Startle.

The effects of permethrin (PRM) and deltamethrin (DLM) on acoustic or light prepulse inhibition of the acoustic startle response (ASR) and tactile startle response (TSR) were studied in adult male Sprague Dawley rats. Preliminary studies were conducted to optimize the parameters of light and acoustic prepulse inhibition of ASR and TSR. Once these parameters were set, a new group of rats was administered PRM (0 or 90mg/kg) or DLM (0 or 25mg/kg) by gavage in 5mL/kg corn oil. ASR and TSR were assessed using acoustic or light prepulses 6, 8, and 12h after PRM and 2, 4, and 6h after DLM exposure. PRM increased ASR 6h post-treatment with no interaction with acoustic prepulse levels and with no effect on TSR. When light was used as the prepulse, PRM increased ASR and TSR at 6h with no interaction with prepulse levels. DLM decreased ASR and TSR on trials without prepulses but not on trials with acoustic prepulses. DLM also decreased ASR when light prepulses were present 4h post-treatment. A final experiment assessed whether the house light in the test cabinet affected ASR and TSR after PRM or DLM exposure. Rats had increased ASR and TSR when house lights were on compared with when they were off, but lighting did not differentially interact with PRM or DLM. Light and acoustic prepulses of ASR and TSR have different effects depending on the test agent and the test parameters.

Vagus Nerve Stimulation Ameliorates Cognitive Impairment and Increased Hippocampal Astrocytes in a Mouse Model of Gulf War Illness

Gulf war illness (GWI), is a chronic multi-symptom illness that has impacted approximately one-third of the veterans who served in the 1990 to 1991 Gulf War. GWI symptoms include cognitive impairments (eg, memory and concentration problems), headaches, migraines, fatigue, gastrointestinal and respiratory issues, as well as emotional deficits. The exposure to neurological chemicals such as the anti-nerve gas drug, pyridostigmine bromide (PB), and the insecticide permethrin (PER), may contribute to the etiologically related factors of GWI. Various studies utilizing mouse models of GWI have reported the interplay of these chemical agents in increasing neuroinflammation and cognitive dysfunction. Astrocytes are involved in the secretion of neuroinflammatory cytokines and chemokines in pathological conditions and have been implicated in GWI symptomology. We hypothesized that exposure to PB and PER causes lasting changes to hippocampal astrocytes, concurrent with chronic cognitive deficits that can be reversed by cervical vagus nerve stimulation (VNS). GWI was induced in CD1 mice by injecting the mixture of PER (200 mg/kg) and PB (2 mg/kg), i.p. for 10 consecutive days. VNS stimulators were implanted at 33 weeks after GWI induction. The results show age-related cognitive alterations at approximately 9 months after exposure to PB and PER. The results also showed an increased number of GFAP-labeled astrocytes in the hippocampus and dentate gyrus that was ameliorated by VNS.

Therapeutic Effects of Curcumin on Toxicity Induced by Permethrin in Rat Liver and SK-Hep-1 Cells

This investigation aimed to evaluate the toxic effects of permethrin (PMN) on rat liver and the therapeutic efficacy of curcumin (CMN) against PMN-induced alterations in hepatic biomarkers, liver antioxidant enzymes, and SK-Hep-1 cells. The animals were divided into four groups of six as follows: the first group was defined as the control, while the second, the third, and the fourth groups were orally treated with PMN (62.5 mg/kg bw), CMN (120 mg/kg bw), and PMN plus CMN, respectively for three weeks. Biochemical markers in the serum and the levels of lipid peroxidation (LPO) and antioxidant enzyme activity in the liver were determined. PMN exposure stimulated significant changes in animals’ hepatic biomarkers, including alanine and aspartate aminotransferases (ALT and AST) and alkaline phosphatase (ALP). The results indicated that LPO was significantly raised in PMN-treated rats, as evidenced by high liver malondialdehyde (MDA) concentration. The antioxidant system in PMN-treated rats was altered, which confirmed by a significant decline (p&lt;0.05) in the activity of catalase (CAT), glutathione peroxidase (GPX), and glutathione-S-transferase (GST) in the liver. On the other hand, the administration of CMN with PMN significantly (p&lt; 0.05) ameliorated ALT, AST, ALP, MDA, CAT, GPX, and GST activity. In addition, CMN demonstrated protective activity against toxicity induced by PMN in SK-Hep-1 cells. In conclusion, our findings demonstrated that PMN induced hepatic damage in rats and CMN had noticeable therapeutic effects on hepatic injuries, oxidative stress, and cytotoxicity induced by PMN.

Flavonoid-rich fraction attenuates permethrin-induced toxicity by modulating ROS-mediated hepatic oxidative stress and mitochondrial dysfunction ex vivo and in vivo in rat.

The present study explores the antioxidant, anti-microbial, and hepatoprotective potentials of flavonoid-rich fractions from Fumaria officinalis against permethrin-induced liver damage ex vivo/in vivo in rat. However, HPLC-DAD analysis revealed the richness of 6 components in ethyl acetate fraction (EAF) where ferulic acid, rosmarinic acid, and myricetin are the most abundant. The in vitro assays showed that EAFs have impressive antioxidant and anti-microbial properties. Ex vivo, permethrin (PER) (100μM) induced a decrease of hepatic AST and ALT activities and 25-OH vitamin D and vitamin C levels and an increase of ALP and LDH activities, TBARS, and ϒ-GT levels with a disturbance of oxidative status. The hepatoprotective effect of EAF (1mg/mL) against PER was confirmed by the amelioration of oxidative stress profile. In vivo, permethrin was found to increase absolute and relative liver weights, plasma transaminase activities, lactate-to-pyruvate ratio, hepatic and mitochondrial lipid peroxidation, and protein oxidation levels. This pesticide triggered a decrease of Ca2+ and Mg2+-ATPases and mitochondrial enzyme activities. The co-treatment with EAF reestablished the hepatic and mitochondrial function, which could be attributed to its richness in phenolic compounds.

Permethrin induced arterial retention of native and oxidized LDL in rats by promoting inflammation, oxidative stress and affecting LDL receptors, and collagen genes

This study is the first to examine the possible mechanism by which long-term exposure to permethrin (PER) can promote arterial retention of proatherogenic lipid and lipoproteins and related vascular dysfunction in rats. Experimental animals were administered two doses of oral PER, PER-1 (2.5 mg/kg/bw) and PER-2 (5 mg/kg/bw), for 90 consecutive days. The results indicated that both PER-1 and PER-2 increased plasmatic and aortic total cholesterol, low-density lipoprotein cholesterol (LDL-C), apo B-100, and oxidized LDL together with arterial scavenger LDL receptors (CD36) but markedly reduced plasmatic and hepatic high-density lipoprotein cholesterol and native LDL receptors in aortic and hepatic tissue. The levels of malondialdehyde, protein carbonyl, and reactive oxygen species were significantly higher, and glutathione content as well as catalase, superoxide dismutase, and glutathione peroxidase activities were suppressed in the aorta of the PER-1 and PER-2 groups. The arterial oxidative damage possibly caused by PER was clearly demonstrated by hematoxylin and eosin histological analysis. Moreover, PER treatment aggravated the inflammatory responses through enhancement of the production of proinflammatory cytokines (tumor necrosis factor–α, interleukin-2, and interleukin-6) in both plasma and aorta. Furthermore, PER-1 and PER-2 potentiated the dysregulation of the aortic extracellular matrix (ECM) content by increasing mRNA activation of collagens I and III. The abundant histological collagen deposition observed in the media and adventitia of intoxicated rats using Masson's trichrome staining corroborates the observed change in ECM. These data showed that oxidative stress related to PER exposure increases the arterial accumulation of lipoprotein biomarkers, likely by actions on both LDL and CD36 receptors, together with the disruption of the aortic ECM.

Protective Effects of Echium amoenum on Oxidative Stress and Gene Expression Induced by Permethrin in Wistar Rats

Background: Echium amoenum (E. amoenum), as one of the most popular plants in Iran, is traditionally used to treat different types of disorders. Objectives: This experimental study aimed to evaluate the modulatory effects of E. amoenum on permethrin (PMN)-induced oxidative stress in rats and to determine the cytoprotective effect of E. amoenum on PMN in SK-Hep-1 cells. Methods: Twenty-four male Wistar rats were randomly divided into four equal groups, including the control (normal saline), orally treated PMN (125 mg/kg of PMN), E. amoenum (100 mg/kg), and E. amoenum + PMN groups for 28 days. The levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), lipid peroxidation (LPO), catalase (CAT), and glutathione peroxidase (GPx), as well as the expression of catalase (CAT) and glutathione peroxidase (GPx), were measured in the liver of all rats. Also, the cytoprotective effect of E. amoenum against PMN was evaluated in the treated SK-Hep-1 cells. Results: The results indicated that LPO increased significantly in the PMN-treated group, as evidenced by the high concentration of malondialdehyde (MDA) in the liver. Alterations of the antioxidant system were also confirmed by the significant decline in CAT and GPx activities (2.9 ± 0.14 and 0.5 ± 0.03, respectively; P &lt; 0.05) and the significant downregulation of CAT (0.4 ± 0.02 folds) and GPx (0.3 ± 0.01 folds) mRNA expression in the liver (P &lt; 0.05). PMN also stimulated significant changes in hepatic biomarkers and induced pathological changes in the liver. On the other hand, administration of E. amoenum significantly reduced abnormalities in biochemical markers, LPO, antioxidant enzymes, gene expression, and pathological complications induced by PMN (P &lt; 0.05). E. amoenum also exhibited cytoprotective effects against cytotoxicity induced by PMN in SK-Hep-1 cells. Conclusions: The present results demonstrated that E. amoenum has significant antioxidant, gene-regulating, and cytoprotective effects.

Modeling the behavioral and metabolic phenotype of mice exposed to Gulf War toxicants

Gulf War Illness (GWI) is a chronic multi‐symptom condition that still affects a third of veterans who served in the 1991 Persian Gulf War (GW). Latently‐emerging and persistent symptoms fall into 5 general domains: neurological/cognition/mood (memory, concentration, anxiety, depression), muscle/joint pain, respiratory, gastrointestinal disturbances and especially chronic fatigue. GWI remains untreated due its poorly understood etiology and pathophysiology. It is suggested that GWI is a result of continuous exposure to GW agents administered to protect military personnel: 1) acetylcholinesterase inhibitor pyridostigmine bromide (PB) taken orally as prophylaxis against nerve agents, 2) topical insecticide permethrin (PER), and 3) topical insect repellent diethyltoluamide (DEET). Although GW agents were administered at safe doses, their chronic and combined use, in addition to stress, a critical component of GW deployment, may produce and/or intensify the pathophysiology of GWI for reasons not fully understood. Additionally, GW veterans report symptoms associated with delayed‐onset Type II diabetes mellitus, which may be associated with chronic fatigue. To further investigate the behavioral, metabolic manifestations of GWI pathophysiology, we studied the effects of acute (AE) and chronic (CE) GW toxicant exposure in adult C57Bl/6N males utilizing a repeated measures design. The AE model consisted of 1wk exposure to PB (2 mg/kg/d; ip), PER (200 mg/kg/d in 70% ETOH; top), DEET (40 mg/kg/d in ETOH; top) and 5 min restraint stress/d (n=4–7). The CE model consisted of 5 days/week for 28 days of exposure to PB (13 mg/kg/d; po), PER (1.3 mg/kg/d; top) in 70% ETOH, DEET (40 mg/kg/d in ETOH; top) and stress 5min/d (n=6–8). A sham control was also tested in CE experiments. Behavioral and metabolic endpoints were measured at one week post treatment (PT) and 60d PT (AE) and 90d PT (CE) to model the delayed and persistent effects seen in GW veterans. When compared to pre‐treatment, GW mice exposed to CE paradigm showed depressive‐like behavior on forced swim, tail suspension and hanging wire tests at post‐treatment. On elevated platform (SUOK) test AE and CE produced sensorimotor alterations as measured by an increased number segments crossed CE decreased missteps/segments crossed relative to pre‐treatment. Increased anxiety was observed as decreased risk assessment (CE) and increased vegetative behavior in AE on SUOK and in AE and CE as less percent time spent in open arm of an elevated plus maze. GW agent exposure had no effect on three‐chambered sociability test. Both CE and AE groups displayed transient but marked insulin insensitivity relative to pre‐treatment. These results show that GW agents can produce insulin insensitivity along with altered sensorimotor integration, anxiety and depressive‐like behavior. In comparison to GW effects on anxiety which persisted at 90d PT (with the exception of vegetative behavior), the depressive‐like effects normalized at 90d PT. Our findings will help inform studies that aim to elucidate the etiology and pathophysiology of GWI.Support or Funding InformationAmerican Physiological Society (AB) and UC Minigrant (AB and JT).

Assessment of matrix effect in quantitative milk analysis for pyrethroids based on GC-MS/MS

In chromatographic analysis of complex samples, the chromatographic responses attributed to pesticides may undergo changes caused by matrix components. These variations can be due by the phenomenon named matrix effect. Cyfluthrin (CYF), cypermethrin (CYP), deltamethrin (DEL), and permethrin (PER) were extracted from raw milk and analysis carried out using a Gas Chromatography coupled to mass spectrometry (GC-MS/MS) technique. The aim of the present work was to investigate the variations of chromatographic response when milk samples are diluted with different solvents (acetone, acetonitrile or hexane) in final dilution immediately after the extraction. Results showed differences between solvents (p&lt;0.05) and acetonitrile showed more appropriate results for all pyrethroids.

Susceptibility of the Danish housefly, Musca domestica Linné to pyrethroid.

The insecticidal activity of a new pyrethroid, fenvalerate, and the effects of its synergists were evaluated using te 49-s and 381-s strains from Denmark which are both resistant to pyrethroid. It was found that the effect of fenvalerate was poor on the pyrethroid-resistant strains and little was expected from the addition of its synergists. Rapid development of resistance was observed in the 49-s strain during the selection with permethrin.

Neurochemical and neuroinflammatory perturbations in two Gulf War Illness models: Modulation by the immunotherapeutic LNFPIII

Gulf War Illness (GWI) manifests a multitude of symptoms, including neurological and immunological, and approximately a third of the 1990–1991 Gulf War (GW) veterans suffer from it. This study sought to characterize the acute neurochemical (monoamine) and neuroinflammatory profiles of two established GWI animal models and examine the potential modulatory effects of the novel immunotherapeutic Lacto-N-fucopentaose III (LNFPIII). In Model 1, male C57BL/6 J mice were treated for 10 days with pyridostigmine bromide (PB) and permethrin (PM). In Model 2, a separate cohort of mice were treated for 14 days with PB and N,N-Diethyl-methylbenzamide (DEET), plus corticosterone (CORT) via drinking water on days 8–14 and diisopropylfluorophosphate (DFP) on day 15. LNFPIII was administered concurrently with GWI chemicals treatments. Brain and spleen monoamines and hippocampal inflammatory marker expression were examined by, respectively, HPLC-ECD and qPCR, 6 h post treatment cessation. Serotonergic (5-HT) and dopaminergic (DA) dyshomeostasis caused by GWI chemicals was apparent in multiple brain regions, primarily in the nucleus accumbens (5-HT) and hippocampus (5-HT, DA) for both models. Splenic levels of 5-HT (both models) and norepinephrine (Model 2) were also disrupted by GWI chemicals. LNFPIII treatment prevented many of the GWI chemicals induced monoamine alterations. Hippocampal inflammatory cytokines were increased in both models, but the magnitude and spread of inflammation was greater in Model 2; LNFPIII was anti-inflammatory, more so in the apparently milder Model 1. Overall, in both models, GWI chemicals led to monoamine disbalance and neuroinflammation. LNFPIII co-treatment prevented many of these disruptions in both models, which is indicative of its promise as a potential GWI therapeutic.

Uji efikasi insektisida pirethroid sintetik berbahan aktif d-allethrin dan permethrin terhadap Aedes aegypti dengan aplikasi pengasapan

Aedes aegypti, vector of DHF, control has been relied on insecticides to prevent the disease transmission. Vector resistance will be speeded up by frequent use of insecticides; therefore alternative insecticides should be sought and tested. In this study, an efficacy test of insecticide containing active ingredient of d-allethrin 10% and permethrin 20% against caged Ae. aegypti hang indoor and outdoor was conducted by thermal fogging application. Both concentrations of 5 ml and 7,5 ml by product per liter diesel oil showed a knockdown effect of about 98 – 100% in less than 60 minutes. After 24 hours holding period at the laboratory about 98 – 100% of Ae.aegypti mortality was observed. It was concluded that the insecticide was effective in killing Ae. aegypti.

Acute embryonic exposure of zebrafish to permethrin induces behavioral changes related to anxiety and aggressiveness in adulthood

Permethrin (PM) is one of the most used synthetic pyrethroid worldwide. Exposure to this compound during pregnancy and early childhood has been indicated as a risk factor for neurodevelopmental disorders. We evaluated the long-term effects of embryonic PM exposure in different stages of zebrafish development. Briefly, embryos (3 hpf) were exposed to sub-lethal concentrations of PM (25 and 50 μg.L−1) during 24 h and then behavioral parameters were evaluated during embryonic (28 hpf), eleutheroembryonic (3 dpf), larval (7 dpf), and adult stages (90 dpf). PM exposure decreased spontaneous movement at 28 hpf and decreased thigmotaxis in eleutheroembryos. The long-term effects of PM include changes in non-motor behaviors such as fear and anxiety in larva and adults. Adults embryonically exposed to PM also showed a significant increase in aggressiveness parameters. These results demonstrated that embryonic exposure to PM induces persistent neurotoxic effects in adulthood, which can impair the cognitive and behavioral fitness of non-target species contributing to a rise in neurodevelopmental disorders.

Acute Exposure to Permethrin Modulates Behavioral Functions, Redox, and Bioenergetics Parameters and Induces DNA Damage and Cell Death in Larval Zebrafish

Permethrin (PM) is a synthetic pyrethroid insecticide widely used as domestic repellent. Damage effects to nontarget organisms have been reported, particularly in the early stages of development. Studies indicate redox unbalance as secondary PM effect. Therefore, our goal was to investigate the acute PM effects on larval zebrafish. Larvae (6 days postfertilization) were exposed to PM (25–600 μg/L) during 24 hours, and 50% lethal concentration was estimated. For subsequent assays, the sublethal PM concentrations of 25 and 50 μg/L were used. PM increased anxiety-like behaviors according to the Novel Tank and Light-Dark tests. At the molecular level, PM induced increased ROS, which may be related to the increased lipid peroxidation, DNA damage, and apoptosis detected in PM-exposed organisms. In parallel, upregulation of the antioxidant system was detected after PM exposure, with increased superoxide dismutase, glutathione S-transferase and glutathione reductase activities, and thiol levels. The increased of Nrf2 target genes and the activation of an electrophile response element-driven reporter Tg(EPRE:LUC-EGFP) suggest that the Nrf2 pathway can mediate a fast response to PM, leading to antioxidant amplification. By using high-resolution respirometry, we found that exposure to PM decreased the oxygen consumption in all respiratory stages, disrupting the oxidative phosphorylation and inhibiting the electron transfer system, leading to decrease in bioenergetics capacity. In addition, PM led to increases of residual oxygen consumption and changes in substrate control ratio. Glucose metabolism seems to be affected by PM, with increased lactate dehydrogenase and decreased citrate synthase activities. Taken together, our results demonstrated the adverse effects of acute sublethal PM concentrations during larval development in zebrafish, causing apparent mitochondrial dysfunction, indicating a potential mechanism to redox unbalance and oxidative stress, which may be linked to the detected cell death and alterations in normal behavior patterns caused by acute PM exposure.