Cypermethrin Research Articles

Environmentally relevant exposure to cypermethrin aggravates diet-induced diabetic symptoms in mice: The interaction between environmental chemicals and diet

Pyrethroids, a class of widely used insecticides, have been linked to diabetes. However, it remains unclear whether and how environmentally relevant exposure to pyrethroids aggravates diet-induced diabetic symptoms. In this study, we investigated the diabetogenic effects of exposure to environmentally relevant doses of cypermethrin (CP), one of the most commonly used pyrethroids, and a high calorie diet (HCD) in adult male mice. Notably, HCD consumption significantly facilitated the bioaccumulation of CP in the liver. CP exposure at the lowest dose in the range of human daily intake exacerbated HCD-induced insulin resistance. In HCD-fed mice, CP treatment significantly decreased hepatic glucose uptake by impairing the translocation of glucose transporter GLUT2. CP exposure regulated hepatic AKT2/GSK3β/GYS2 pathway, thereby reducing glycogenesis and stimulating gluconeogenesis in the livers of HCD-fed mice. Hepatic transcriptome data showed that CP exposure of HCD-fed mice increased hepatic expression of thioredoxin-interacting protein (Txnip) and vanin-1 (VnnI) genes, which were involved in regulating GLUT2 translocation and AKT2/GSK3β/GYS2 pathway activity, respectively. CP treatment significantly decreased hepatic glucose uptake in HCD-fed mice by impairing the translocation of glucose transporter GLUT2, which was modulated by upregulation of TXNIP. CP exposure regulated hepatic AKT2/GSK3β/GYS2 pathway through upregulation of VNNI, thereby reducing glycogenesis and stimulating gluconeogenesis in the livers of HCD-fed mice. This is the first study to show that HCD led to an enrichment of lipophilic CP in the liver, which significantly disrupted glucose homeostasis and caused prediabetic phenotype. Our findings suggest that when assessing the health risks of lipophilic environmental chemicals, especially for metabolism-related outcomes, the interaction between contaminants and diet factors should be considered, otherwise the health risks may be underestimated.

Kuersetin'in Sipermetrin Kaynaklı Mide Hasarı Üzerine Etkileri: Oksidatif Stres, Enflamasyon ve Apoptozun Rolü

This study was conducted to investigate the effects of quercetin (QUE) on cypermethrin (CYP) induced gastrotoxicity in rats. 35 Sprague-Dawley rats were randomly divided into five groups, 7 in each group. In the study, 25 and 50 mg/kg QUE were administered orally 30 min after 25 mg/kg cypermethrin was administered to rats for 28 days. Oxidative stress, inflammation, ER stress, apoptosis and autophagy markers were biochemically analyzed in gastric tissues. Additionally, histological analysis was performed for microscopic evaluation of gastric tissue. The results revealed that QUE prevented tissue damage by reducing CYP-induced lipid peroxidation (MDA) and increasing GSH, SOD, CAT and GPx activities. It also showed anti-inflammatory effect by suppressing inflammatory markers such as NF-𝜅B, IL-1β, TNF-α, iNOS and COX-2. QUE administration down-regulated CYP-induced increased PERK, ATF6, Caspase-3 and Beclin-1 markers. In addition, administration of QUE ameliorated the pathological tissue damage in gastric tissue due to CYP. The data of this study show that Que suppresses CYP-induced gastric toxicity by reducing oxidative stress, inflammation, ER stress, apoptosis a autophagy.

Astaxanthin protects oocyte maturation against cypermethrin-induced defects in pigs

Cypermethrin (CYP), a pyrethroid insecticide, exerts the detrimental effect on the reproductive system, while astaxanthin (AST), a xanthophyll carotenoid, possesses the powerful antioxidant property and can protect oocyte maturation. However, the toxicity of CYP and the protective role of AST against CYP during oocyte maturation remain unclear. Here, porcine oocytes were applied to investigate the potential effects and underlying mechanisms of CYP and AST during oocyte maturation. This work demonstrated that CYP significantly decreased oocyte maturation rate and subsequent embryo development in a dose-dependent manner (P < 0.05). And, CYP obviously induced the overproduction of reactive oxygen species and the reduction of glutathione content by downregulating the expression of redox genes in oocytes (P < 0.05). Moreover, CYP significantly caused oocyte DNA damage and disturbed the function of endoplasmic reticulum by altering the transcription of DNA damage repair and endoplasmic reticulum stress related genes (P < 0.05). Whereas CYP-exposed oocytes were treated with AST, these defects caused by CYP were significantly ameliorated (P < 0.05). In conclusion, this study demonstrated that CYP exerted the toxic effect on porcine oocytes, while AST effectively alleviated CYP-induced defects. This work provides a potential strategy to prevent pesticide toxicity and protect oocyte maturation in mammalian reproduction.

Multiomics implicate gut microbiota in low cypermethrin (CP) exposure induced multiorgan toxicological effects in pubertal male rats

Cypermethrin (CP), widely used as a broad-spectrum pesticide, has raised concerns over its frequent presence in the environment and potential health risks. The present study focused on incorporating the gut-organ axis theory to reinterpret the toxicological effects and mechanisms following CP exposure at environmentally relevant concentrations (0.1 mg/kg/d and 0.5 mg/kg/d) in pubertal male rats. The results showed alterations in histopathological and organosomatic indices in the liver, brain, and epididymis. Through multiomics network analysis, it was found that Lachnospiraceae and Ruminococcaceae may contribute to the alteration in serum L-carnitine and trigonelline, leading to hepatic lipid accumulation following CP exposure. Additionally, Ruminococcaceae, Lachnospiraceae, and Porphyromonadaceae were associated with CP-induced glutamatergic hypofunction and overproduction of TNF-α, potentially contributing to the brain neurotoxicity. Overall, the study provides important insights into the potential mechanisms underlying CP-induced toxicity and highlights the need for continued research to fully understand the implications for CP-induced health risks. The incorporation of the gut-organ axis theory in the study provides a promising avenue for future research into the potential interactions between gut microbiota and organ toxicity, and the potential for targeted interventions to mitigate the adverse effects of environmental toxins.

Kinetics of uptake and depuration of synthetic pyrethroid insecticides in manila clam (Ruditapes philippinarum).

Synthetic pyrethroid insecticides (SPIs) are frequently detected in water bodies and sediments, and they show high toxicity to aquatic organisms, but their toxicity kinetics remain unknown. In this work, the kinetics of uptake and depuration of three SPIs, fenpropathrin (FP), cypermethrin (CM) and deltamethrin (DM) were evaluated in manila clams (Ruditapes philippinarum) for the first time through a bioconcentration-semi-static test. Clams were exposed to three SPIs of different concentrations (2 ng/mL and 20 ng/mL) for 4 days, followed by a 10-day depuration stage. The results indicated that adult manila clams could absorb SPIs rapidly, and the bioconcentration factor (BCF) values of SPIs were different at high and low concentrations of contaminants. The depuration rate constants (k2) of SPIs in adult manila clams ranged from 0.024 h-1 to 0.037 h-1. The bioaccumulation factors ranged from 319.41 to 574.38. And the half-lives (t1/2) were in the range of 18.49 to 29.22 h. These results showed that manila clams have a high bioconcentration capacity, and SPIs have a high cumulative risk for bivalves. Moreover, after 10 days of elimination, SPIs can still be detected in manila clams at all concentrations, indicating that the complete elimination of SPIs required a longer time.

MicroRNA‑30a‑5p regulates cypermethrin-induced apoptosis of Sertoli cells by targeting KLF9 in vitro

Cypermethrin (CYP) has been identified as one kind of endocrine-disrupting chemicals (EDCs) to induce male reproduction damage. This study aimed to investigate the effects and mechanisms of miR-30a-5p on CYP induced apoptosis of TM4 mouse Sertoli cells in vitro. In the present study, 0 μM, 10 μM, 20 μM, 40 μM and 80 μM CYP were used to treat TM4 cells for 24 h. The apoptosis of TM4 cells, the expression level of miR-30a-5p, the protein expressions and the interaction between miR-30a-5p and KLF9 were detected by flow cytometry, quantitative Real-Time PCR, Western blot and luciferase reporter assays. CYP induced apoptosis of TM4 cells, inhibited expression of miR-30a-5p in TM4 cells, and overexpression of miR-30a-5p partially recovered CYP induced cells apoptosis. Furthermore, KLF9 was a potential downstream target of miR-30a-5p predicted by publicly available databases. KLF9 expression level in TM4 cells was significantly elevated after treatment with CYP, and the induction was inhibited by miR-30a-5p mimics transfection. Meanwhile, dual-luciferase reporter assay demonstrated that miR-30a-5p directly targeted KLF9–3′UTR. Moreover, in the presence of CYP, the apoptosis regulator p53 expression was also increased in TM4 cells. Overexpression miR-30a-5p or down-regulation of KLF9 both attenuated the induction of CYP on p53 expression. Overall, the present study demonstrated that miR-30a-5p regulated CYP induced TM4 cells apoptosis by targeting KLF9/p53 axis.

Early-Life Exposure to Commercial Formulation Containing Deltamethrin and Cypermethrin Insecticides Impacts Redox System and Induces Unexpected Regional Effects in Rat Offspring Brain.

Several studies have shown that the oxidative impact of pesticides is most prevalent in rural environments where they are intensively used. At different levels, pyrethroids are reported to promote neurodegeneration; they share the ability to promote oxidative stress, and to induce mitochondrial impairments, α-synuclein overexpression and neuronal cell loss. The present study evaluates the impact of early-life exposure to a commercial formulation containing deltamethrin (DM) and cypermethrin (CYP) at a dose of 1/100 LD50 (1.28 and 2.5 mg/kg, respectively). Rats aged 30 days old, treated from the 6th to the 21st day of life, were tested for brain antioxidant activity and α-synuclein levels. Four regions of the brain were analyzed: the striatum, cerebellum, cortex and hippocampus. Our data demonstrated a significant increase in catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) antioxidant levels in the brain regions compared to the controls. Pups exhibited no significant changes in protein carbonyl levels and lipid peroxidation. Striatal α-synuclein expression was significantly reduced in the rats exposed to DM + CYP, while the treatment resulted in a non-significant increase in the other brain areas. These findings indicate unexpected effects of postnatal treatment with the commercial formulation containing DM and CYP on brain redox state and α-synuclein expression, suggesting an adaptive response.

Cypermethrin induced liver oxidative DNA damage via the JNK/c-Jun pathway

To clarify the adverse effect of cypermethrin(CYP) on the liver and explore the underlying role of the MAPK pathway. Twenty-four Sprague-Dawley(SD) rats were exposed to 0, 5, 10 and 20 mg/(kg·d) β-CYP by gavage for 31 days. Histomorphological and ultrastructural changes were evaluated by the hematoxylin &amp; eosin(HE) staining and transmission electron microscope(TEM). Levels of MDA and 8-OHdG were detected by ELISA. Expressions of p-JNK and γ-H2A. X were assessed by IHC and IF respectively. RT-PCR was performed to examine mRNA levels of GPx1, GPx4, SOD1, and SOD2 in rat testes. Western blot was conducted to determine protein expressions of GPx1, SOD2, CAT, γ-H2A. X, and the MAPK pathway-associated proteins in rat testes. After β-CYP exposure, the histomorphology and ultrastructures of rat livers were abnormally altered, as evidenced by hepatic sinusoidal dilation, hepatic plate space formation, mitochondrial crest fracture, etc. Moreover, β-CYP induced mRNA levels of GPx1, GPx4, SOD1 and SOD2, as well as protein expressions of GPx1 and SOD2 in the liver. Compared to the control, GPx1 and SOD2 protein expressions were decreased by 57.9% and 50.0%(P&lt;0.05), whereas the MDA level was increased by 56.2%(P&lt;0.05) in the high-dose group. Additionally, the JNK/c-Jun pathway, one of MAPK pathways, in the liver was activated by β-CYP, as shown by the increase of JNK and c-Jun phosphorylation, and protein expressions of p-JNK and p-c-Jun in the high-dose group were elevated by 47.7% and 46.5%(P&lt;0.05) in comparison to the control, but the ERK and p38 pathways were not affected after β-CYP exposure. Furthermore, β-CYP promoted 8-OHdG and γ-H2A. X expressions in the liver. Compared to the control, γ-H2A. X protein expression in the mid-and high-dose group was upregulated by 16.9% and 33.9%(P&lt;0.05), respectively. Cypermethrin had detrimental effects on the liver. CYP not only directly altered liver histomorphology and ultrastructures, but also caused oxidative stress, which activated the JNK/c-Jun pathway, finally inducing the DNA damage.

Dose- and dosage-dependent spectrum of respiratory toxicity of cypermethrin in rabbits

Pyrethroids are popular insecticides. Shortness of breath and dyspnea are key signs of exposure; however, their respiratory effects are rarely studied. This study investigated the combination and ratios of specific blood tests and lung lesions as respiratory effects of cypermethrin (CY) in rabbits. The effects of CY at various doses and times are the novelty of this study. Doses (50, 100, and 150 mg.kg-1 body weight) of CY were injected intraperitoneally every week for up to 9 weeks in rabbits assigned into four equal groups. Data analysis revealed various respiratory signs, significantly (p ≤ 0.05) lower fibrinogen, higher neutrophils-lymphocytes (NL), LDH-lymphocytes (LL), and De-Ritis ratios (DR), and lesions in the lungs. The frequency and incidence of these effects were dose and dosage dependent. The CY leads to pulmonary signs and allergic effects. Lung injury increases cell-free heme in plasma, causing pulmonary edema with hemolysis. Emphysema and fibrosis followed the migration of basophils and mononuclear cells to the lungs. This study inferred that CY exposure caused lower fibrinogen, higher NL, LL, and DR ratios, and pulmonary lesions, which forecast poor immunity, especially increased risk for cardiac and lung diseases.

Systematic Toxicity of Cypermethrin and Alterations in Behavior of Albino Rats.

The present study aimed to evaluate the effect of repeatedly orally administering cypermethrin (CYP) at different doses on the behavior, hematology, and histology of adult male and female albino rats for 1 month. For this, animals have divided into four different groups and each group contained 10 animals (5 males and 5 females). Group I served as a control group and groups II, III, and IV were represented as experimental groups and treated with CYP at doses of 25, 50, and 75 mg/kg body weight/day/rat, respectively. Through the behavioral results of this study, it was observed that cypermethrin intoxication causes dose-dependent moderate to high toxicity symptoms like vomiting, decreased food consumption, thick eye discharge, rolling, tremors, loss of coordination, tilted neck, and convulsion attacks. A significant reduction in body weight of high-dose (75 mg)-treated animals, especially in females, was noticed. Similarly, hematological data also revealed that CYP exposure caused a reduction in the level of Hb, RBC, WBC, neutrophil, and other blood indices such as PCV and MCV and an increase in the lymphocyte percentage in both male and female experimental groups. Microscopic observation stated that CYP produced infiltration of cells near the central vein, hepatocyte degeneration, congestion of the central and portal veins, hemorrhage, and necrosis in liver tissue. Shrinkage of the glomerulus, necrosis in the glomerulus and renal tubules, congestion of blood cells, and hemorrhage were seen in kidney tissue. The current study suggests that hepatotoxicity and nephrotoxicity due to cypermethrin exposure were more prominent in female rats.

Development of insecticide-impregnated polyester/cotton blend fabric and assessment of their repellent characteristics against Cimex lectularius and dengue vectors Aedes albopictus and Aedes aegypti

BackgroundPersonal protection measures using insecticide-treated fabric is one of the most effective strategies to prevent the bites of hematophagous insects. Many countries have had success treating fabrics with pyrethroids on an individual level.MethodsIn the current study, a new combination of insecticides, alpha-cypermethrin (ACP) and deltamethrin (DET), has been impregnated on fabric composed of a 50:50 blend of polyester and cotton. Residual and morphological analysis was performed along with the evaluation of physical parameters. Biological evaluations were performed to check the repellency, knockdown, and mortality of insecticide-impregnated fabric (IIF) against bed bugs (Cimex lectularius) using Petri plate assay and mosquitoes (Aedes aegypti and Aedes albopictus) using cone bioassay.ResultsThe results showed the repellency of IIF to be 56.6% for C. lectularius and a knockdown percentage of 53.3% and 63.3% for Ae. aegypti and Ae. albopictus, respectively. A > 80% mortality was found for both species of mosquitoes up to 20 cycles of washing with no significant difference (P > 0.05). From high-performance liquid chromatography (HPLC) analysis, the reduction in the contents of ACP and DET after subsequent washes can be correlated with the overall decrease in bioefficacy. ACP and DET remaining in unit gram of fabric after 20 wash cycles were found to be 5.4 mg and 3.1 mg, respectively. By examining the fabric’s surface morphology using scanning electron microscope (SEM) and utilizing energy-dispersive x-ray (EDX) analysis, it was possible to identify the presence of insecticides that were adhered to the fabric. Differential scanning calorimetry (DSC) showed distinctive endothermic peak of insecticide at 98.3 ºC, whereas no change in thermal behavior was observed from thermo-gravimetric analysis (TGA). Furthermore, the physical attributes of IIF provide conclusive evidence for its firmness.ConclusionAll experimental findings were consistent with the potential use of IIF as a bed bug- and mosquito-repellent fabric to be used against hematophagous infestations. This fabric can serve as a potential strategy to control vector-borne diseases like dengue, malaria, trench fever, etc.Graphical

Reduced synergistic efficacy of piperonyl butoxide in combination with alpha-cypermethrin in vitro in an insecticide-resistant strain of the sheep blowfly, Lucilia cuprina

Control of flystrike on sheep relies on the use of insecticides. The present study used in vitro assays to examine the potential for increasing the efficacy of synthetic pyrethroids against sheep blowfly larvae using the synergist piperonyl butoxide (PBO). We examined the potency of alpha-cypermethrin (ACP) / PBO combinations against a reference insecticide-susceptible strain (LS) and a field-derived strain showing resistance to dicyclanil and imidacloprid. Co-treatment of the insecticide-susceptible strain with ACP/PBO resulted in increasing levels of synergism as the PBO concentration was increased, with synergism ratios (SRs) of up to 114-fold. Treatment with PBO/ACP combinations at ratios of 20:1 and 5:1 resulted in significant levels of synergism: SRs of 13.5- and 7.6-fold, respectively. However, the levels of synergism were significantly less for the insecticide-resistant strain: SRs of 4.6- and 2.6-fold for the 20:1 and 5:1 ratios, respectively. The resistant strain showed no resistance to ACP when administered alone, however, was 2-fold less sensitive than the LS strain to the toxic effects of PBO alone. This insensitivity to PBO was removed by co-treatment with the P450 inhibitor aminobenzotriazole, suggesting an increased level of P450-mediated metabolism of the PBO in this strain compared to the LS strain, and hence providing a likely explanation for the reduced synergistic efficacy of PBO on ACP toxicity in the resistant strain. While PBO was able to synergise ACP with both of the blowfly strains examined here, the reduced synergistic efficacy observed with the field-derived insecticide-resistant strain lessens the potential usefulness of such a combination for blowfly control in the field.

Acaricides containing zein nanoparticles: A tool for a lower impact control of the cattle tick Rhipicephalus microplus

Nanoformulations containing zein nanoparticles (ZN) can promote the stability and protection of molecules with acaricidal activity. The present study sought to develop nanoformulations with ZN associated with cypermethrin (CYPE) + chlorpyrifos (CHLO) + a plant compound (citral, menthol or limonene), characterize them, and verify their efficacy against Rhipicephalus microplus ticks. Additionally, we aimed to assess its safety in nontarget nematodes found in soil at a site subjected to contamination by acaricides. The nanoformulations were characterized by dynamic light scattering and nanoparticle tracking analysis. Nanoformulations 1 (ZN+CYPE+CHLO+citral), 2 (ZN+CYPE+CHLO+menthol), and 3 (ZN+CYPE+CHLO+limonene) were measured for diameter, polydispersion, zeta potential, concentration, and encapsulation efficiency. Nanoformulations 1, 2, and 3 were evaluated in a range from 0.004 to 0.466 mg/mL on R. microplus larvae and caused mortality > 80% at concentrations above 0.029 mg/mL. The commercial acaricide Colosso® (CYPE 15 g + CHLO 25 g + citronellal 1 g) was evaluated also from 0.004 to 0.512 mg/mL and resulted in 71.9% larval mortality at 0.064 mg/mL. Formulations 1, 2, and 3 at 0.466 mg/mL showed acaricidal efficacy of 50.2%, 40.5%, and 60.1% on engorged females, respectively, while Colosso® at 0.512 mg/mL obtained only 39.4%. The nanoformulations exhibited long residual period of activity and lower toxicity to nontarget nematodes. ZN was able to protect the active compounds against degradation during the storage period. Thus, ZN can be an alternative for the development of new acaricidal formulations using lower concentrations of active compounds.

Modeling the Effects of Cypermethrin Toxicity on Ovalbumin-Induced Allergic Pneumonitis Rats: Macrophage Phenotype Differentiation and p38/STAT6 Signaling Are Candidate Targets of Pirfenidone Treatment

Although the classic form of asthma is characterized by chronic pneumonitis with eosinophil infiltration and steroid responsivity, asthma has multifactorial pathogenesis and various clinical phenotypes. Previous studies strongly suggested that chemical exposure could influence the severity and course of asthma and reduce its steroid responsiveness. Cypermethrin (CYP), a common pesticide used in agriculture, was investigated for the possible aggravation of the ovalbumin (OVA)-induced allergic pneumonitis and the possible induction of steroid resistance in rats. Additionally, it was investigated whether pirfenidone (PFD) could substitute dexamethasone, as an alternative treatment option, for the induced steroid resistance. Fifty-six male Wistar albino rats were randomly divided into seven groups: control, PFD alone, allergic pneumonitis, CYP alone, allergic pneumonitis/CYP-exposed, allergic pneumonitis/CYP/dexamethasone (Dex), and allergic pneumonitis/CYP/PFD-treated groups. Allergic pneumonitis was induced by three intraperitoneal OVA injections administered once a week, followed by an intranasal OVA instillation challenge. CYP (25 mg/kg/d), Dex (1 mg/kg/d), and PFD (100 mg/kg/d) were administered orally from day 15 to the end of the experiment. Bronchoalveolar lavage fluid (BALF) was analyzed for cytokine levels. Hematoxylin and eosin (H&E) and periodic acid Schiff (PAS)-stained lung sections were prepared. Immunohistochemical identification of p38 MAPK and lung macrophages was performed. The inflammatory/oxidative status of the lung and PCR-quantification of the STAT6, p38 MAPK, MUC5AC, and IL-13 genes were carried out. The allergic pneumonitis-only group showed eosinophil-mediated inflammation (p < 0.05). Further CYP exposure aggravated lung inflammation and showed steroid-resistant changes, p38 activation, neutrophil-mediated, M1 macrophage-related inflammation (p < 0.05). All changes were reversed (p < 0.05) by PFD, meanwhile not by dexamethasone treatment. Pirfenidone could replace dexamethasone treatment in the current rat model of CYP-induced severe steroid-resistant asthma via inhibiting the M1 macrophage differentiation through modulation of the STAT6/p38 MAPK pathway.

Bio-efficacy of aluminum phosphide and cypermethrin against some physiological and biochemical aspects of Chrysomya megacephala maggots

Carrion flies play a significant role in forensic entomotoxicology, where they are employed as alternative samples when traditional samples are unavailable. In situations of poisoned death, these toxins disrupt insect development and affect forensic entomology analyses. So, forensic entomotoxicologists must be aware of this impact. The present study aimed to determine the effects of aluminum phosphide (AlP) and cypermethrin (CP) on the biochemical parameters and antioxidant enzymes of the third instar of Chrysomya megacephala maggots. C. megacephala was reared on normal and poisoned rabbit carcasses with aluminum phosphide and cypermethrin. The third larval instar of C. megacephala was studied using by spectrophotometer for detection of total protein, (TP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione s-transferase (GST), catalase (CAT) and malondialdehyde (MDA). The results indicated to significantly decrease of TP, TAC, SOD, GST and CAT and increase of AST, ALT and MDA in the maggots reared on the poisoned carcasses with AlP or CP compared with control group. In conclusion, the tested insecticides brought about a decrease antioxidant enzyme activity and increase of MDA could be involved in free radicals in C. megacephala larvae leading to oxidative stress by these insecticidal components.

Neuroprotective Effects of Nano-Curcumin against Cypermethrin Associated Oxidative Stress and Up-Regulation of Apoptotic and Inflammatory Gene Expression in Rat Brains.

Cypermethrin (CPM) is the most toxic synthetic pyrethroid that has established neurotoxicity through oxidative stress and neurochemical agitation in experimental rats. The toxic effects are supposed to be mediated by modifying the sodium channels, reducing Na-K ATPase, acetylcholine esterase (AchE), and monoamine oxidase (MAO). The use of curcumin nanoparticles (NC) that have potent antioxidant, anti-inflammatory and antiapoptotic properties with improved bioavailability attenuates neurotoxicity in rat brains. To test this hypothesis, animals were divided into five groups, each having six animals. Group-I control received vehicle only, while Group-II was treated with 50 mg/kg CPM. Group-III and Group-IV received both CPM and NC 2.5 mg/kg and 5 mg/kg, respectively. Group-V received 5 mg of NC alone. The CPM and NC were given by oral route. Afterwards, brain antioxidant status was measured by assessing lipid peroxidation (LPO), 4-HNE, glutathione reduced (GSH), antioxidant enzyme catalase, and superoxide dismutase (SOD) along with neurotoxicity markers Na-K ATPase, AchE, and MAO. Inflammation and apoptosis indices were estimated by ELISA, qRT-PCR, and immunohistochemistry, while morphologic changes were examined by histopathology. Observations from the study confirmed CPM-induced neurotoxicity by altering Na-K ATPase, AchE, and MAO, and by decreasing the activity of antioxidant enzymes and GSH. Oxidative stress marker LPO and the level of inflammatory interleukins IL-6, IL-1β, and TNF-α were notably high, and elevated expressions of Bax, NF-kB, and caspase-3 and -9 were reported in CPM group. However, NC treatment against CPM offers protection by improving antioxidant status and lowering LPO, inflammation, and apoptosis. The neurotoxicity marker's enzyme successfully attenuated after NC treatment. Therefore, this study supports the administration of NC effectively ameliorated CPM-induced neurotoxicity in experimental rats.

Enhancing the Toxicity of Cypermethrin and Spinosad against Spodoptera littoralis (Lepidoptera: Noctuidae) by Inhibition of Detoxification Enzymes.

The extensive use of wide-ranging insecticides in agricultural activities may develop resistance in insects. The dipping technique was utilized for examining changes in detoxifying enzyme levels in Spodoptera littoralis L. induced by cypermethrin (CYP) and spinosad (SPD) with and without a combination of three enzyme inhibitors: triphenyl phosphate (TPP), diethyl maleate (DEM), and piperonyl butoxide (PBO), at 70 μg/mL. PBO, DEM, and TPP showed 50% mortality against larvae at 236.2, 324.5, and 245.8 μg/mL, respectively. The LC50 value of CYP on S. littoralis larvae reduced from 2.86 μg/mL to 1.58, 2.26, and 1.96 μg/mL, while the LC50 value of SPD declined from 3.27 μg/mL to 2.34, 2.56, and 2.53, with the addition of PBO, DEM, and TPP, respectively, 24 h after treatment. Moreover, the activity of carboxylesterase (CarE), glutathione S-transferase (GST), and cytochrome P450 monooxygenase (Cyp 450) was significantly inhibited (p < 0.05) by TPP, DEM, PBO plus CYP, and SPD in S. littoralis larvae in comparison with tested insecticides alone. These findings suggested that three enzyme inhibitors play a major role in increasing the toxicity of CYP and SPD in S. littoralis and will provide insight into how to overcome insecticide resistance in insects.

Simultaneous and Sensitive Detection of Three Pesticides Using a Functional Poly(Sulfobetaine Methacrylate)-Coated Paper-Based Colorimetric Sensor.

Chlorpyrifos (CHL), profenofos (PRO) and cypermethrin (CYP) are widely used in combination to increase crop yields. However, these three pesticides can cause serious harm to human health and do not easily degrade. In this study, a novel visible paper sensor has been prepared successfully and different colorimetric reactions were utilized to detect the three pesticides simultaneously. The sensor was constructed by grafting a zwitterionic polymer onto a cellulose filter (CF) and placing it on a glass surface modified with PDMS. The branch shape was designed to form multiple detection areas, which were modified with specific pesticides and corresponding chromogenic reagents. The as-prepared colorimetric platform exhibited high sensitivity, a short detection time, a good linear response and a low detection limit (LOD) for the three pesticides (chlorpyrifos: y = 46.801 - 1.939x, R2 = 0.983, LOD = 0.235 mg/L; profenofos: y = 40.068 + 42.5x, R2 = 0.988, LOD = 4.891 mg/L; cypermethrin: y = 51.993 + 1.474x, R2 = 0.993, LOD = 4.053 mg/L). The comparison of the results obtained by the proposed paper sensor and those obtained by spectrophotometry further revealed the stability and reliability of the paper sensor. In particular, the color intensity of the interaction between the pesticides and coloring agents could be directly observed by the human eye. The consistency of the colorimetric/optical assay was proven in real target pesticide samples. Thus, this sensing strategy provides a portable, cost-effective, accurate and visualized paper platform, which could be suitable for application in the fruit and vegetable industry for monitoring CHL, PRO and CYP in parallel.

Mixture effects of thiamethoxam and seven pesticides with different modes of action on honey bees (Aplis mellifera)

Even though honey bees in the field are routinely exposed to a complex mixture of many different agrochemicals, few studies have surveyed toxic effects of pesticide mixtures on bees. To elucidate the interactive actions of pesticides on crop pollinators, we determined the individual and joint toxicities of thiamethoxam (THI) and other seven pesticides [dimethoate (DIM), methomyl (MET), zeta-cypermethrin (ZCY), cyfluthrin (CYF), permethrin (PER), esfenvalerate (ESF) and tetraconazole (TET)] to honey bees (Aplis mellifera) with feeding toxicity test. Results from the 7-days toxicity test implied that THI elicited the highest toxicity with a LC50 data of 0.25 (0.20–0.29) μg mL−1, followed by MET and DIM with LC50 data of 4.19 (3.58–4.88) and 5.30 (4.65–6.03) μg mL−1, respectively. By comparison, pyrethroids and TET possessed relatively low toxicities with their LC50 data from the range of 33.78 (29.12–38.39) to 1125 (922.4–1,442) μg mL−1. Among 98 evaluated THI-containing binary to octonary mixtures, 29.59% of combinations exhibited synergistic effects. In contrast, 18.37% of combinations exhibited antagonistic effects on A. mellifera. Moreover, 54.8% pesticide combinations incorporating THI and TET displayed synergistic toxicities to the insects. Our findings emphasized that the coexistence of several pesticides might induce enhanced toxicity to honey bees. Overall, our results afforded worthful toxicological information on the combined actions of neonicotinoids and current-use pesticides on honey bees, which could accelerate farther comprehend on the possible detriments of other pesticide mixtures in agro-environment.

In silico and in vivo assessment of developmental toxicity, oxidative stress response & Na+/K+-ATPase activity in zebrafish embryos exposed to cypermethrin

Cypermethrin (CYP), a synthetic type II pyrethroid pesticide, is extensively used to control pests in industrial, domestic, and agricultural environments. However, its indiscriminate use leads to a potential threat to aquatic organisms. Although several reports focussed on developmental toxicity effects, a concise study combining cardiotoxicity along with Na+/K+-ATPase activity and molecular docking of developmental proteins with CYP was lacking. This present study was designed to address this gap to comprehend the impact of CYP exposure (0, 25, 100 and 200 µg/L) on embryonic zebrafish. As a result, CYP delayed the hatching rate, reduced heart rate, increased mortality rate and induced numerous morphological abnormalities. Subsequently, CYP induced oxidative stress in treated zebrafish embryos with the concomitant increase in antioxidant enzymes (SOD and CAT) and malondialdehyde production. In addition, an alteration in AChE, NO content and Na+/K+-ATPase activity was observed, suggesting a disruption in cardiac development and ion regulation. Furthermore, AO staining showed notable apoptotic cells which are supported by alteration in apoptosis-related gene expressions. Moreover, to explore the putative targets of CYP, computational docking with developmental proteins (WNT3A, WNT8A, GATA-4, Nkx 2–5 and ZHE1) showed strong interactions and binding. Taken together, our findings provide a better understanding of assessing the ecotoxicological risk information and the mode of action underlying the development of teleost fishes following CYP exposure. Meanwhile, the pioneering nature of this study is to emphasize the future use of Na+/K+-ATPase activity as a potential toxicity biomarker and in silico molecular docking studies to complement developmental toxicity findings.