Permethrin Research Articles

Targeting ERK/COX-2 signaling pathway in permethrin-induced testicular toxicity: a possible modulating effect of matrine.

Permethrin (PER), the prevalent synthetic pyrethroid, was reported to have genotoxic effects along with male reproductive organs impairment. Matrine, the Chinese herb chief alkaloid constituent, is used extensively owing to its recognized pharmacological properties. The study included 30 rats allocated equally into three groups; Group I: Control group, Group II: PER group and Group III: Matrine treated PER group. All groups were subjected to the measurement of Steroidogenic acute regulatory (StAR) gene expression by PCR technique while testosterone, phosphorylated Extracellular signal-regulated Kinase 1/2 (p-ERK1/2) and Cyclooxygenase 2 (COX-2) levels were assessed by ELISA technique. Malondialdehyde (MDA), total antioxidant capacity (TAC) and glutathione peroxidase (GPx) were also detected spectrophotometrically in addition to assessment of DNA fragmentation. Testicular histological structure as well as sperm count and morphology were studied. Matrine improved testicular toxicity evidenced by significant upregulation of StAR gene expression, elevation of testosterone level and significant decrease of p-ERK1/2 and COX-2 levels. Moreover, enhancements of the antioxidant status together with improvement of the histological findings were observed. These findings could pave the way for matrine to be used as a promising therapeutic agent in treatment of PER toxicity.

Positive effect of an electrolyzed reduced water on gut permeability, fecal microbiota and liver in an animal model of Parkinson's disease.

There is growing awareness within the scientific community of the strong connection between the inflammation in the intestine and the pathogenesis of Parkinson’s disease (PD). In previous studies we developed a PD animal model exposing pup rats to permethrin (PERM) pesticide. Here, we intended to explore whether in our animal model there were changes in gut permeability, fecal microbiota and hepatic injury. Moreover, we tested if the co-treatment with an electrolyzed reduced (ERW) was effective to protect against alterations induced by PERM. Rats (from postnatal day 6 to 21) were gavaged daily with PERM, PERM+ERW or vehicle and gut, liver and feces were analyzed in 2-months-old rats. Increased gut permeability, measured by FITC-dextran assay, was detected in PERM group compared to control and PERM+ERW groups. In duodenum and ileum, concentration of occludin was higher in control group than those measured in PERM group, whereas only in duodenum ZO-1 was higher in control than those measured in PERM and PERM+ERW groups. Number of inflammatory focis and neutrophils as well as iNOS protein levels were higher in livers of PERM-treated rats than in those of PERM+ERW and control rats. Fecal microbiota analysis revealed that Lachnospira was less abundant and Defluviitaleaceae more abundant in the PERM group, whereas the co-treatment with ERW was protective against PERM treatment since the abundances in Lachnospira and Defluviitaleaceae were similar to those in the control group. Higher abundances of butyrate- producing bacteria such as Blautia, U.m. of Lachnospiraceae family, U.m. of Ruminococcaceae family, Papillibacter, Roseburia, Intestinimonas, Shuttleworthia together with higher butyric acid levels were detected in PERM+ERW group compared to the other groups. In conclusion, the PD animal model showed increased intestinal permeability together with hepatic inflammation correlated with altered gut microbiota. The positive effects of ERW co-treatment observed in gut, liver and brain of rats were linked to changes on gut microbiota.

A permethrin metabolite is associated with adaptive immune responses in Gulf War Illness

Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood and liver of pyridostigmine bromide (PB) and PER (PB+PER) exposed mice at acute and chronic post-exposure timepoints. We tested whether 3-PBA-haptenated albumin (3-PBA-albumin) can activate immune cells since it is known that chemically haptenated proteins can stimulate immune responses. We detected autoantibodies against 3-PBA-albumin in plasma from PB + PER exposed mice and veterans with GWI at chronic post-exposure timepoints. We also observed that in vitro treatment of blood with 3-PBA-albumin resulted in the activation of B- and T-helper lymphocytes and that these immune cells were also increased in blood of PB + PER exposed mice and veterans with GWI. These immune changes corresponded with elevated levels of infiltrating monocytes in the brain and blood of PB + PER exposed mice which coincided with alterations in the markers of blood-brain barrier disruption, brain macrophages and neuroinflammation. These studies suggest that pesticide exposure associated with GWI may have resulted in the activation of the peripheral and CNS adaptive immune responses, possibly contributing to an autoimmune-type phenotype in veterans with GWI.

High-throughput analysis of insecticides on malaria vectors using liquid chromatography tandem mass spectrometry.

BackgroundDifferent setups and protocols have been developed for investigating insecticide effects on Anopheles (An.) mosquitoes, vectors of malaria. However, chemical uptake resulting from their tarsal contact with insecticide-treated material has seldom been investigated. To address the challenges encountered in the interpretation of bioassay data, a high throughput method for chemical analysis on malaria vectors was developed and validated for five selected insecticides including alpha-cypermethrin (aCYP), deltamethrin (DM), etofenprox (EPX), permethrin (PM), pirimiphos-methyl (PPM).MethodsThe method includes a single chemical extraction step via an ultrasound probe on mosquito samples and analysis via liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-MS/MS). The protocol was established for two malaria vector species, Anopheles gambiae senso stricto (s.s.) and An. stephensi, both males and females. Recovery rates ranged from 70 to 100% without any influence of sex or species. The method was efficiently applied to female An. gambiae s.s. of the KISUMU1 reference strain, after susceptibility tests using the World Health Organization’s standard protocol.ResultsSusceptibility tests revealed 13.4–18.4 minutes knockdown times for 50% mosquitoes during exposure to EPX and pyrethroids. The mortality rates 24 hours post-exposure to insecticides were mostly 99–100%, except in two PM and three PPM assays suggesting possible or confirmed resistance to these insecticides. The mean insecticide uptake in dead mosquitoes ranged from 23 pg (aCYP) to 1812 pg (EPX) per specimen. However, the mean uptake in survivors to PM and PPM was reduced by at least 25%, suggesting that acute doses were not achieved in these specimens during bioassays.ConclusionsThe developed and validated UHPLC-MS/MS method could be used to address some limitations of bioassays or to assess the penetration of insecticides in mosquito matrix with reference to cuticle thickness and other insecticide resistance mechanisms.

Age Dependency of Blood-Brain Barrier Penetration by cis- and trans-Permethrin in the Rat.

Permethrin (PER), a type I pyrethroid, is the most widely used insecticide in domestic settings in the United States. The overall objective of this study was to assess the efficiency of the blood-brain barrier (BBB) as an obstacle to the 14C-cis-permethrin (CIS) and 14C-trans-permethrin (TRANS) isomers of PER, and to determine whether its barrier function changes during maturation of the rat. Experiments were conducted to quantify brain uptake of CIS and TRANS in postnatal day 145, 21, and 90 Sprague-Dawley rats. The common carotid artery of anesthetized rats was perfused for 2 or 4 minutes with 1, 10, or 50 µM 14C-CIS or 14C-TRANS in 4% albumin. Brain deposition of each isomer was inversely related to age, with levels in the youngest animals >5 times those in adults. Brain uptake was linear over the 50-fold range of pyrethroid concentrations, indicative of passive, nonsaturable BBB permeation. The extent of uptake of toxicologically relevant concentrations of CIS and TRANS was quite similar. Thus, dissimilar BBB permeation does not contribute to the greater acute neurotoxic potency of CIS, but greater permeability of the immature BBB to CIS and TRANS may contribute to the increased susceptibility of preweanling rodents to the insecticides.

Gulf War agents pyridostigmine bromide and permethrin cause hypersensitive nociception that is restored after vagus nerve stimulation

Gulf war illness (GWI) is a chronic multi-symptom disease that afflicts 25–33% of troops that were deployed in the 1990–1991 Gulf War. GWI symptoms include cognitive, behavioral and emotional deficits, as well as migraines and pain. It is possible that exposure to Gulf War agents and prophylactics contributed to the reported symptomology. Pyridostigmine bromide (PB) and permethrin (PER) were given to protect from nerve gas attacks and insect vector born disease, respectively. Previous studies have demonstrated that 10 days of exposure to these chemicals can cause symptoms analogous to those observed in GWI, including impairment of long-term memory in mice. Other studies using this model have shown chronic neuroinflammation, and chronic neuroinflammation can lead to altered nociceptive sensitivity. At 10-weeks after the 10-day PB and PER exposure paradigm, we observed lowered nociceptive threshold on the Von Frey test that was no longer evident at 28 weeks and 38 weeks post-exposure. We further determined that vagus nerve stimulation, initiated at 38 weeks after exposure, restores the lowered nociceptive sensitivity. Therefore, stimulating the vagus nerve appears to influence nociception. Future studies are need to elucidate possible mechanisms of this effect.

Metabolomics-on-a-chip approach to study hepatotoxicity of DDT, permethrin and their mixtures.

Despite the diversity of studies on pesticide toxicities, there is a serious lack of information concerning the toxic effect of pesticides mixtures. Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are among the most prevalent pesticides in the environment and have been the subject of several toxicological studies. However, there are no data on the toxicity of their mixtures. In this study, we used an approach combining cell culture in microfluidic biochips with gas chromatography-mass spectrometry metabolomics profiling to investigate the biomarkers of toxicity of DDT, PMT and their mixtures. All parameters observed indicated that no significant effect was observed in hepatocytes cultures exposed to low doses (15μm) of DDT and PMT. Conversely, combined low doses induce moderate oxidative stress and cell death. The toxic signature of high doses of pesticides (150μm) was illustrated by severe oxidative stress and cell mortality. Metabolomics profiling revealed that hepatocytes exposure to DDT150, PMT150 and DDT150 and PMT150 cause important modulation in intermediates of glutathione pathway and tricarboxylic acid cycle, amino acids and metabolites associated to hepatic necrosis and inflammation (α-ketoglutarate, arginine and 2-hydroxybutyrate). These changes were more striking in the combined group. Finally, DDT150 led to a significant increase of benzoate, decanoate, octanoate, palmitate, stearate and tetradecanoate, which illustrates the estrogen modulation. This study demonstrates the potential of metabolomics-on-a-chip approach to improve knowledge on the mode of action of pesticides.

Early life exposure of zebrafish (Danio rerio) to synthetic pyrethroids and their metabolites: a comparison of phenotypic and behavioral indicators and gene expression involved in the HPT axis and innate immune system.

Ecotoxicological studies have revealed the association between synthetic pyrethroid (SP) exposure and aquatic toxicity in fish; however, research on the toxic effects of SP metabolites is still limited. In this study, the toxicity of two SPs (permethrin (PM) and β-cypermethrin (β-CP)) and their three metabolites (3-phenoxybenzoic alcohol (PBCOH), 3-phenoxybenzaldehyde (PBCHO), and 3-phenoxybenzoic acid (PBCOOH)) towards zebrafish embryos and larvae was evaluated. Both SPs and their metabolites exhibited significant developmental toxicities, caused abnormal vascular development, and changed locomotor activities in larvae. The alteration of gene expression involved in the thyroid system and the innate immune system indicated that SPs and their three metabolites have the potency to induce thyroid disruption and trigger an immune response. The results from the present study suggest that SP metabolites could induce multiple toxic responses similar to parent compounds, and their toxicity should be considered for improving the understanding of environmental risks of SPs.

Effects of DDT and permethrin on rat hepatocytes cultivated in microfluidic biochips: Metabolomics and gene expression study

Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are amongst most prevalent pesticides in the environment. Although their toxicity has been extensively studied, molecular mechanisms and metabolic effects remain unclear, including in liver where their detoxification occurs. Here, we used metabolomics, coupled to RT-qPCR analysis, to examine effects of DDT and PMT on hepatocytes cultivated in biochips. At 150 μM, DDT caused cell death, cytochrome P450 induction and modulation of estrogen metabolism. Metabolomics analysis showed an increase in some lipids and sugars after 6 h, and a decrease in fatty acids (tetradecanoate, octanoate and linoleate) after 24 h exposure. We also found a change in expression associated with genes involved in hepatic estrogen, lipid, and sugar metabolism. PMT at 150 μM perturbed lipid/sugar homeostasis and estrogen signaling pathway, between 2 and 6 h. After 24 h, lipids and sugars were found to decrease, suggesting continuous energy demand to detoxify PMT. Finally, at 15 μM, DDT and PMT appeared to have a small effect on metabolism and were detoxified after 24 h. Our results show a time-dependent perturbation of sugar/lipid homeostasis by DDT and PMT at 150 μM. Furthermore, DDT at high dose led to cell death, inflammatory response and oxidative stress.

Core-Shell Nanoparticles/Two-Dimensional (2D) Hexagonal Boron Nitride Nanosheets with Molecularly Imprinted Polymer for Electrochemical Sensing of Cypermethrin

Cypermethrin ([RS]-alpha-cyano-3-phenoxybenzyl [1RS, 3RS; 1RS, 3SR]-3-[2,2-dichlorovinyl]-2,2-dimethylcyclopropanecarboxylate) is a crucial pyrethroid and it is generally used as poison against crop pests, domestic insects and ectoparasites in farmed fish. A new molecular imprinted sensor approach based on core-shell type nanoparticles (Fe@AuNPs) incorporated two-dimensional (2D) hexagonal boron nitride (2D-hBN) nanosheets was presented for cypermethrin (CYP) detection in wastewater samples. All nanomaterials’ formation and properties were highlighted with scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) method, energy dispersive X-ray analysis (EDX), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). CYP imprinted voltammetric sensor was improved in presence of 80.0 mM phenol containing 20.0 mM CYP by CV. 1.0 × 10−13 - 1.0 × 10−8 M and 3.0 × 10−14 M were founded as the linearity range and the detection limit (LOD). Finally, CYP imprinted glassy carbon electrode (GCE) was used for wastewater sample analysis in presence of the other competitor agents such as deltamethrin (DEL), tetrametrin (TET) and permethrin (PER). In addition, the prepared sensor was investigated in terms of stability and repeatability.

Anxiety, neuroinflammation, cholinergic and GABAergic abnormalities are early markers of Gulf War illness in a mouse model of the disease

Gulf War Illness (GWI) is a chronic disease that affects the 1991 Gulf War (GW) veterans for which treatment is lacking. It has been hypothesized that drugs used to protect military personnel from chemical attacks and insects during the war: pyridostigmine bromide (PB),N, N-diethyl-m-toluamide (DEET), and permethrin (PER) together with stress may have contributed collectively and synergistically to generate GWI. There is a need to find markers of pathology to be used in pre-clinical trials. For this purpose we employed a previously validated mouse model of GWI evoked by daily exposure to PB (1.3 mg/kg), DEET (40 mg/kg), PER (0.13 mg/kg), and 5 min of restraint stress for 28 days to analyze behavior, brain pathology and neurochemical outcomes three months later. GWI-model mice were characterized by increased anxiety, decreased hippocampal levels of N-acetyl aspartate, GABA, the GABA-producing enzyme GAD-67 and microglial activation. We also observed that GWI model was sexually dimorphic on some measures: males had increased while females had decreased protein levels of the acetylcholine-synthesizing enzyme, choline acetyltransferase, in the septum and hippocampus and decreased levels of the receptor for brain-derived neurotrophic factor, TrkB140, in the hippocampus. Increased hippocampal levels of nerve growth factor were detected in males only. Together the data show behavioral and neuropathological abnormalities detected at 3 months post-exposure and that some of them are sexually dimorphic. Future preclinical studies for GWI may take advantage of this short latency model and should include both males and females as their response to treatment may differ.

Environmentally relevant levels of λ-cyhalothrin, fenvalerate, and permethrin cause developmental toxicity and disrupt endocrine system in zebrafish (Danio rerio) embryo

Synthetic pyrethroids (SPs) are one of the most widely used pesticides and frequently detected in the aquatic environment. Previous studies have shown that SPs posed high aquatic toxicity, but information on the developmental toxicity and endocrine disruption on zebrafish (Danio rerio) at environmentally relevant concentrations is limited. In this study, zebrafish embryos were employed to examine the adverse effects of λ-cyhalothrin (LCT), fenvalerate (FEN), and permethrin (PM) at 2.5, 10, 25, 125, 500 nM for 96 h. The results showed these 3 SPs caused dose-dependent mortality, malformation rate, and hatching rate. Thyroid hormone triiodothyronine (T3) levels were significantly decreased after exposure to LCT and FEN. Quantitative real-time PCR analysis was then performed on a series of nuclear receptors (NRs) genes involved in the hypothalamic–pituitary–gonadal (HPG), hypothalamic–pituitary–thyroid (HPT), hypothalamic–pituitary–adrenocortical (HPA) axes, and oxidative-stress-related system. Our results showed that LCT, FEN, and PM downregulated AR expression while upregulated ER1 expression, and caused alteration to ER2a and ER2b expression. As for the expression of TRα and TRβ, they were both decreased following exposure to the 3 SPs. LCT and PM downregulated the MR expression and FEN induced MR expression. In addition, the expression of GR was increased after treating with LCT, while it was suppressed after exposure to FEN and PM. The 3 SPs also caused various alterations to the expression of genes including AhRs, PPARα, and PXR. These findings suggest that these 3 SPs may cause developmental toxicity to zebrafish larvae by disrupting endocrine signaling at environmentally relevant concentrations.

Complementary proteomic approaches reveal mitochondrial dysfunction, immune and inflammatory dysregulation in a mouse model of Gulf War Illness

PurposeLong‐term consequences of combined pyridostigmine bromide (PB) and permethrin (PER) exposure in C57BL6/J mice using a well‐characterized mouse model of exposure to these Gulf War (GW) agents were explored at the protein level.Experimental designWe used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane‐bound protein fractions from brain samples using two orthogonal isotopic labeling LC‐MS/MS proteomic approaches—stable isotope dimethyl labeling and iTRAQ.ResultsThe use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure.Conclusions and clinical relevanceThe work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation. Collectively, our work identified key pathways which were chronically impacted in the mouse CNS following acute GW agent exposure, this may lead to the identification of potential targets for therapeutic intervention in the future.Long‐term consequences of combined PB and PER exposure in C57BL6/J mice using a well‐characterized mouse model of exposure to these GW agents were explored at the protein level. Expanding on earlier work, we used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane‐bound protein fractions from brain samples using two orthogonal isotopic labeling LC‐MS/MS proteomic approaches—stable isotope dimethyl labeling and iTRAQ. The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation at 5 months postexposure to PB + PER.

Subchronic toxicity of low dose propoxur, permethrin, and their combination on the redox status of rat liver

Carbamates and pyrethroids are widely used pesticides. However, their joint toxicity at low doses with long-term exposure remains unknown. Therefore, we investigated the subchronic joint hepatotoxicity of the two representative pesticides within these two classes, i.e., propoxur (PR) and permethrin (PE) in rats. The male Wistar rats were orally treated with three different doses of PR, PE and their mixtures for 90 consecutive days. Liver weight, serum clinical chemistry parameters and histopathological changes were measured to access the hepatotoxicity. In addition, oxidative stress markers in liver were measured using biochemical assays. The results showed that PR reduced liver weight and lead to prominent liver histological changes. Moreover, PR dose-dependently induced lipid peroxidation and reduced superoxide dismutase activity. In contrast, PE induced a relatively mild hepatotoxicity. Intriguingly, the mixture of PR and PE did not reduce liver weight or increase serum aspartate transaminase activity. In addition, the mixture did not reduce the antioxidant enzyme activity as PR did. Thus, these results showed that PR induced prominent hepatotoxicity with subchronic exposure, and there is a potential antagonistic interaction between PR and PE on the oxidative damage in liver of rats.

Neurotoxicity and oxidative stress induced by permethrin in gills of the freshwater mussel Unio ravoisieri

ABSTRACTPyrethroids are contaminants found in the aquatic environment, and their toxicological effects on aquatic organisms have received extensive attention. However, the impact on freshwater bivalve of exposure to these chemicals is still largely unknown. Freshwater mussels Unio ravoisieri were exposed to two nominal permethrin (PM) concentrations C1 = 50 µg/L and C2 = 100 µg/L during 7 days. The measured concentrations of PM using gas chromatography (GC/ECD) in the treated aquariums were, respectively, 28.7–62.3 µg/L. Catalase (CAT), Glutathione-S-transferase (GST), and Acetylcholinesterase (AChE) activities, Glutatione (GSH) and Malondialdehyde (MDA) levels were determined in gills of U. ravoisieri. Significant increase in CAT activity by the lowest concentration and decrease by highest concentration were observed. Additionally, GST activity was increased in a concentration-dependent manner. However, statistically significant decrease in GSH levels (about 39%) was observed only at high concentration of this compound (100 µg/L). PM generated an increase in MDA levels reaching the highest value at the high concentration. AChE activity of mussel ranging from 51% inhibition at lowest concentration 50 µg/L to 89% inhibition at highest concentration 100 µg/L. The results indicated that oxidative stress and cell damage might be one of the main mechanisms of PM toxicity to freshwater mussels.

In vivo and in silico studies to identify mechanisms associated with Nurr1 modulation following early life exposure to permethrin in rats

The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat’s life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels. Adult rats showed enhanced DNMT3b and α-synuclein aggregation compared to the control group, while with aging a significant decrease in all biomarkers studied was observed. No changes in Nurr1 promoter methylation in adolescent, adult and old rats were found.In silico studies showed clear evidence of a strong binding interaction between PERM and its metabolite 3-phenoxybenzoic acid with the nuclear orphan receptor Nurr1. These findings suggest that an additional interference with the dopaminergic neuron pathway could occur in situ during PERM accumulation in brain.Therefore, Nurr1 modulation in early life PERM-treated rats, depends on age-related adaptive responses in animals.

Permethrin is a potential thyroid-disrupting chemical: In vivo and in silico envidence

Permethrin (PM), one of the most heavily used synthetic pyrethroids, has the potential to interfere with thyroid hormones in mammals, however, the effect is poorly recognized in aquatic organisms. Herein, embryonic zebrafish were exposed to PM (0, 1, 3 and 10μg/L) until 72h post-fertilization. We demonstrated that PM readily accumulated in larvae with a preference for cis-PM, inhibited development and increased thyroxine and 3,5,3′-triiodothyronine levels accompanying increase in the transcription of most target genes, i.e., thyroid-stimulating hormone β, deiodinases, thyroid receptors, involved in the hypothalamic-pituitary-thyroid axis. Further Western blot analysis indicated that transthyretin (TTR) protein was significantly increased. Molecular docking analysis and molecular dynamics simulations revealed that PM fits into three hydrophobic binding pocket of TTR, one of the molecular targets of thyroid hormone disrupting chemicals (THDCs), and forms strong van der Waals interactions with six resides of TTR, including Leu8, Leu 101, Leu125, Thr214, Leu218 and Val229, thus altering TTR activity. Both in vivo and in silico studies clearly disclosed that PM potentially disrupts the thyroid endocrine system in fish. This study provides a rapid and cost-effective approach for identifying THDCs and the underlying mechanisms.

Permethrin-induced oxidative damage in liver of rainbow trout (Oncorhynchus mykiss) and its attenuation by vitamin C.

The objective of this study was to investigate the propensity of permethrin (PTN) to induce oxidative stress and changes in enzyme activities in liver of rainbow trout and its possible attenuation by vitamin C. Forty-eight fish were randomly assigned to 1 of 6 treatment groups and their livers were used for liver perfusion method: control (0 µgL(-1) permethrin and 0 mgL(-1) vitamin C), PTN-0.16 (0.16 µgL(-1) permethrin), PTN-0.32 (0.32 µgL(-1) permethrin), PTN-0.64 (0.64 µgL(-1) permethrin), Vit. C (17.2 mgL(-1) vitamin C), and PTN-0.64 + Vit. C (0.64 µgL(-1) permethrin and 17.2 mgL(-1) vitamin C). Results obtained showed that permethrin significantly (P<0.05) increased ALT, AST and LDH activities in the liver perfusion medium and malondialdehyde (MDA) level in liver tissue. The values of reduced glutathione (GSH) and total antioxidant capacity (FRAP) in the liver tissue were significantly decreased due to permethrin administration. Pearson's correlation analysis revealed a positive correlation between MDA concentration and ALT, AST and LDH activities in the permethrin groups, suggesting that the enhanced lipid peroxidation may be linked to hepatic damage caused by permethrin. On the other hand, treatment with vitamin C in the PTN-0.64 + Vit. C group increased the values of GSH and FRAP, and decreased the level of MDA and the activities of hepatic enzymes, when compared to the PTN-0.64 group. The present study revealed that vitamin C could ameliorate permethrin-induced oxidative damage by decreasing lipid peroxidation and altering antioxidant defense system in liver of rainbow trout.

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.

Efficacy of naringenin against permethrin-induced testicular toxicity in rats.

Permethrin (PM), a synthetic pyrethroid insecticide, has broad toxicity spectra. We aimed to investigate the effects of PM on the testes of adult albino rats, examine the recovery response and evaluate the efficacy of naringenin (NG) supplementation. Adult male albino rats were randomly assigned to five groups of six each: control, NG (50 mg/kg), PM (70 mg/kg), recovery (after subsequent withdrawal of PM) and NG-PM group. All treatments were given by oral gavage for 6 weeks and another 3 weeks for the recovery group. At the time of sacrifice, each testis was weighed. Biochemical analysis of epididymal sperm count and serum testosterone level was performed. Testes were processed for histological, ultrastructural and c-Kit immunohistochemical study. PM toxicity was evidenced by a highly significant decrease in testicular weight, epididymal sperm count and serum testosterone level compared to control. Furthermore, testicular structure abnormalities and reduced c-Kit immunoreactions were observed. Stoppage of PM in the recovery group partially reversed PM-induced changes. There was a mild decrease in testicular weight and biochemical parameters compared to control. The structure of seminiferous tubules was partially retained. The NG-PM group showed an overall improvement in testicular weight and biochemical alterations which were confirmed by light and electron microscopic examination. In conclusion, PM induced testicular toxicity, which was ameliorated by NG co-administration. However, stoppage of PM exposure was associated with partial recovery.