Protective Effects of Coenzyme Q10 on Testicular Histology in Rats Exposed via Chronic Mosquito Coil Smoke Inhalation.

OBJECTIVE: To determine the preventive effect of coenzyme Q10 (CoQ10) on the testicular histology of rats exposed chronically to mosquito coil smoke. STUDY DESIGN: Experimental study. Place and Duration of the Study: Department of Anatomy, Army Medical College/National University of Medical Sciences, Rawalpindi, Pakistan, from January to December 2020. METHODOLOGY: Thirty male Sprague Dawley rats were divided into three groups of 10 rats each. Group A was the healthy control. Group B rats were exposed to allethrin-based mosquito coil smoke for 12 weeks (4 hours/day). Group C rats received coenzyme Q10 (CoQ10, 10mg/kg/day) through oral gavage, in addition to 12 weeks of mosquito coil smoke exposure (4 hours/day). At the end of the study, testicular histology was compared among three groups including the germinal epithelium height, seminiferous tubule diameter, and testicular capsule thickness, while adjusting for the body weight variations among rats. RESULTS: The rats in Group B, exposed only to mosquito coil smoke showed testicular disruption, characterised by dilated seminiferous tubules (p <0.001), reduced germinal epithelial height (p <0.001), and thickened testicular capsule (p <0.007), as compared to the control group rats. However, the germinal epithelium height (p = 0.73) and testicular capsule thickness (p = 0.31) of rats receiving CoQ10 in addition to mosquito coil smoke inhalation were not significantly different from the control group. CONCLUSION: Prolonged inhalation of allethrin-based mosquito coil smoke can cause testicular disruption among rats. The oral CoQ10 administration can effectively prevent the histomorphological adverse effects on the testis among rats exposed to mosquito coil smoke. KEY WORDS: Allethrin, Coenzyme Q10, Germinal epithelium, Mosquito coil, Seminiferous tubules, Testicular capsule.

The Efficacy of a Pyrethroid-impregnated Mattress Liner on Multiple International Strains of Cimex lectularius (Hemiptera: Cimicidae) and Cimex hemipterus (Hemiptera: Cimicidae).

Modern bed bugs are resistant to multiple insecticide classes, particularly the pyrethroids. The efficacy of pyrethroid-impregnated mattress liners marketed for bed bug management has been variable. This study evaluated the efficacy of a permethrin-impregnated mattress liner, ActiveGuard, against 24 bed bug strains, consisting of both Cimex hemipterus (F.) and Cimex lectularius L. A 'mat assay', employing an allethrin-impregnated mat, was used to establish the pyrethroid resistance profile of all strains. Three experiments were conducted to evaluate the effect of ActiveGuard exposure on bed bug knockdown: 1) exposing the bed bugs continuously on the liner for up to 24 d, 2) holding the bed bugs on the liner for either 4 or 6 h, and 3) placing a noninsecticide treated fabric above the liner with the bed bugs held continuously on top. Our results indicated that all modern strains (collected within the last 15 years during the current resurgence) were pyrethroid-resistant, although the magnitude of resistance was highly variable between strains. In the continuous exposure study, an incomplete knockdown was recorded for most modern bed bug strains, with some having no knockdown even up to 7 d of constant exposure. In the 4 or 6 h exposure study, the level of knockdown was reduced even further, and very few bed bugs were knocked down in the double fabric study. The results of this study indicate that pyrethroid-impregnated mattress liners are not likely to be effective in the management of most modern bed bug infestations involving either C. hemipterus or C. lectularius.

The role of pyrethroid derivatives in autophagy and apoptosis crosstalk signaling and potential risk for malignancies.

Pyrethroids and its derivatives widespread and uncontrolled continuous use has influenced multiple deleterious effects resulting in as a potential risk factor causing damage to the organ systems. Allethrin and prallethrin are extensively used yet their influences on human primary cells are very limited or under reported. The potential mechanisms by which allethrin and prallethrin modulates human primary cells, especially the molecular mechanisms or interconnectivity of autophagy-apoptosis, their clinical relevance in human subjects or patients are not well defined. In this current study, we've furnished the evidence that both allethrin and prallethrin user samples significantly induced Ccl2 mRNA expression, increased amount of reactive oxygen intermediate, inhibited membrane bound enzymes and altered membrane fluidity. Pyrethroid derivative users had induced levels of lipid peroxidation and induced binding activities of transcription factors(tfs) like CEBP-ß and NF-AT. Pyrethroid derivatives induced autophagy, elicited intracellular Ca2+ concentration, calcineurin and regulated proapoptotic genes, DAPK1, Bim. Our current study presumably comprises the initial investigation of a very new mechanism of pyrethroid derivatives-moderated programed cell death in various cell sets or types, like human primary cells where-in this is a late event, is documented. Hence, current research-study might be significant in the various pyrethroid derivatives-allied hematological-related cancers and immunosuppressant or auto-immune disorders. In the foremost instance, we present data stating that pyrethroid derivatives induces multiple cell signaling cascades, like CEBP-ß, NF-AT, ERK and MAPK having a role in autophagy thereby; synchronously effectively impact on the apoptosis, therefore causing hematological tumors and toxic or immune related disorders.

Allethrin Promotes Apoptosis and Autophagy Associated with the Oxidative Stress-Related PI3K/AKT/mTOR Signaling Pathway in Developing Rat Ovaries.

The increased concern regarding the reduction in female fertility and the impressive numbers of women undergoing fertility treatment support the existence of environmental factors beyond inappropriate programming of developing ovaries. Among these factors are pyrethroids, which are currently some of the most commonly used pesticides worldwide. The present study was performed to investigate the developmental effects of the pyrethroid-based insecticide allethrin on ovarian function in rat offspring in adulthood. We mainly focused on the roles of oxidative stress, apoptosis, autophagy and the related pathways in ovarian injury. Thirty-day-old Wistar albino female rats were intragastrically administered 0 (control), 34.2 or 68.5 mg/kg body weight allethrin after breeding from Day 6 of pregnancy until delivery. We found that allethrin-induced ovarian histopathological damage was accompanied by elevations in oxidative stress and apoptosis. Interestingly, the number of autophagosomes in allethrin-treated ovaries was higher, and this increase was correlated with the upregulated expression of genes and proteins related to the autophagic marker LC-3. Furthermore, allethrin downregulated the expression of PI3K, AKT and mTOR in allethrin-treated ovaries compared with control ovaries. Taken together, the findings of this study suggest that exposure to the pyrethroid-based insecticide allethrin adversely affects both the follicle structure and function in rat offspring during adulthood. Specifically, allethrin can induce excessive oxidative stress and defective autophagy-related apoptosis, probably through inactivation of the PI3K/AKT/mTOR signaling pathway, and these effects may contribute to ovarian dysfunction and impaired fertility in female offspring.

Bioallethrin-induced generation of reactive species and oxidative damage in isolated human erythrocytes.

Bioallethrin is an insecticide that is widely used to control mosquitoes, fleas and cockroaches. The widespread use of bioallethrin has resulted in both occupational and non-occupational human exposure. Bioallethrin enters blood, regardless of the route of exposure, where it can interact with erythrocytes. We have studied the effect of bioallethrin on isolated human erythrocytes under in vitro conditions. Erythrocytes were incubated with increasing concentrations of bioallethrin (10-200 µM) for 4 h at 37 °C. Several biochemical parameters were analyzed in bioallethrin treated and untreated (control) cells. Incubation of erythrocytes with bioallethrin increased protein oxidation, lipid peroxidation and depleted sulfhydryl group content. Membrane damage was evident from cell lysis, osmotic fragility, inhibition of bound enzymes and transmembrane electron transport system. Bioallethrin also increased hemoglobin oxidation, heme degradation and the release of free iron moiety. This will decrease the oxygen transporting ability of blood. Bioallethrin treatment altered the specific activities of antioxidant enzymes and diminished the antioxidant power of cells. Scanning electron microscopy showed that bioallethrin treatment also altered erythrocyte mophology. Almost all changes were in a bioallethrin concentration dependent manner. The cytotoxicity of bioallethrin is probably mediated by reactive oxygen and nitrogen species whose formation was significantly enhanced in treated erythrocytes. Thus bioallethrin enhances the generation of reactive species which cause oxidative damage of cell components in human erythrocytes.

Laboratory evaluation of three commercial coil products for protection efficacy against Anopheles gambiae from southern Ghana: a preliminary study.

Residents in irrigated urban agricultural sites face numerous mosquito problems such as increased mosquito populations and reduced insecticides susceptibility due to the creation of mosquito breeding sites and agricultural use of insecticides and hence require effective protective products against them. In this study, the protection effectiveness of three pyrethroid formulated mosquito coils of Malaysian origin against Anopheles gambiae sensu lato from an irrigated urban agricultural site in Ghana were evaluated for their potential use. Sucrose fed An. gambiae s.l. were exposed to insecticide-containing coils in a 70 cm x 70 cm x 70 cm glass chamber to assess the insecticidal effect of the coils. The 0.005% metofluthrin coil caused the most rapid knockdown of 50% of the test mosquitoes. The mean lethal effect of the coils on An. gambiae s.l. were as follows; 0.005% metofluthrin (86%), 0.3% d-allethrin (74.33%), 0.15% d-trans allethrin (72%) and the 0.25% d-allethrin reference coil (69%). The 0.005% metofluthrin coil achieved the highest insecticidal effect on An. gambiae s.l. compared to the other coils and hence performed better than the others as an anti-mosquito product. All the three test coils were effective against An. gambaie s.l. from the irrigated agricultural site compared to the reference coil.

Allethrin-Based Mosquito Control Device Causing Knockdown, Morbidity, and Mortality in Four Species of Field-Caught Mosquitoes (Diptera: Culicidae).

A mosquito control device marketed for spatial repellency, the ThermaCELL Mosquito Repellent Appliance, was evaluated in semifield trials against multiple field-caught species of mosquito. Using paper and mesh cages, mosquito test groups of at least 30 mosquitoes were suspended in a 2,337 cubic foot outdoor space while two ThermaCELL repellent devices were active. After 30 min of treatment, cages were moved to the laboratory to observe knockdown, morbidity, and mortality for 24 h. Species tested included Aedes atlanticus Dyar and Knab (98% average mortality), Psorophora ferox Humboldt (97% average mortality), Psorophora columbiae Dyar and Knab (96% average mortality), and Aedes taeniorhynchus Wiedemann (84% average mortality). The repellent devices showed effectiveness with high knockdown and mortality across all species tested. Mosquito control devices like the ThermaCELL Mosquito Repellent Appliance may have further practical applications to help combat viral exposures by limiting host mosquitoes. Such devices may provide a functional alternative to DEET dependence in the current state of mosquito management.

Identification of putative kdr mutations in the tropical bed bug, Cimex hemipterus (Hemiptera: Cimicidae).

BACKGROUND: Bed bugs [both Cimex hemipterus (F.) and Cimex lectularius L.] are highly resistant to pyrethroids worldwide. An important resistance mechanism known as 'knockdown resistance' (kdr) is caused by genetic point mutations on the voltage-gated sodium channel (VGSC) gene. Previous studies have identified two point mutations (V419L and L925I) on the VGSC gene in C. lectularius that are responsible for kdr-type resistance. However, the kdr mutations in C. hemipterus have not been investigated. RESULTS: Four novel mutations, L899V (leucine to valine), M918I (methionine to isoleucine), D953G (aspartic acid to glycine) and L1014F (leucine to phenylalanine), were identified in the domain II region of the C. hemipterus VGSC gene. This region has been widely investigated for the study of kdr-type resistance to pyrethroids in other insect pests. The V419L and L925I kdr mutations as previously identified in C. lectularius were not detected in C. hemipterus. CONCLUSION: M918I and L1014F are considered to be probable kdr mutations and may play essential roles in kdr-type resistance to pyrethroids in C. hemipterus. Further studies are under way in the authors' laboratory to determine the non-kdr-type resistance mechanisms in C. hemipterus.

Insecticidal activity and expression of cytochrome P450 family 4 genes in Aedes albopictus after exposure to pyrethroid mosquito coils.

Mosquito coils are insecticides commonly used for protection against mosquitoes due to their toxic effects on mosquito populations. These effects on mosquitoes could induce the expression of metabolic enzymes in exposed populations as a counteractive measure. Cytochrome P450 family 4 (CYP4) are metabolic enzymes associated with a wide range of biological activities including insecticide resistance. In this study, the efficacies of three commercial mosquito coils with different pyrethroid active ingredients were assessed and their potential to induce the expression of CYP4 genes in Aedes albopictus analyzed by real-time quantitative PCR. Coils containing 0.3 % D-allethrin and 0.005 % metofluthrin exacted profound toxic effects on Ae. albopictus, inducing high mortalities (≥90 %) compared to the 0.2 % D-allethrin reference coil. CYP4H42 and CYP4H43 expressions were significantly higher in 0.3 % D-allethrin treated mosquitoes compared to the other treated populations. Short-term (KT50) exposure to mosquito coils induced significantly higher expression of both genes in 0.005 % metofluthrin exposed mosquitoes. These results suggest the evaluated products provided better protection than the reference coil; however, they also induced the expression of metabolic genes which could impact negatively on personal protection against mosquito.

Nationwide investigation of the pyrethroid susceptibility of mosquito larvae collected from used tires in Vietnam.

Pyrethroid resistance is envisioned to be a major problem for the vector control program since, at present, there are no suitable chemical substitutes for pyrethroids. Cross-resistance to knockdown agents, which are mainly used in mosquito coils and related products as spatial repellents, is the most serious concern. Since cross-resistance is a global phenomenon, we have started to monitor the distribution of mosquito resistance to pyrethroids. The first pilot study was carried out in Vietnam. We periodically drove along the national road from the north end to the Mekong Delta in Vietnam and collected mosquito larvae from used tires. Simplified susceptibility tests were performed using the fourth instar larvae of Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus. Compared with the other species, Ae. aegypti demonstrated the most prominent reduction in susceptibility. For Ae. aegypti, significant increases in the susceptibility indices with a decrease in the latitude of collection points were observed, indicating that the susceptibility of Ae. aegypti against d-allethrin was lower in the southern part, including mountainous areas, as compared to that in the northern part of Vietnam. There was a significant correlation between the susceptibility indices in Ae. aegypti and the sum of annual pyrethroid use for malaria control (1998-2002). This might explain that the use of pyrethroids as residual treatment inside houses and pyrethroid-impregnated bed nets for malaria control is attributable to low pyrethroid susceptibility in Ae. aegypti. Such insecticide treatment appeared to have been intensively administered in the interior and along the periphery of human habitation areas where, incidentally, the breeding and resting sites of Ae. aegypti are located. This might account for the strong selection pressure toward Ae. aegypti and not Ae. albopictus.

Control of mosquito vectors of tropical infectious diseases: (2) pyrethroid susceptibility of Aedes aegypti ( l) collected from different sites in Thailand.

Four strains (SS, BS, A and B) of Aedes aegypti collected from different sites in Bangkok and at different times were examined for their pyrethroid susceptibility. Mosquito coils containing dl, d-T80-allethrin, d, d-T-prallethrin and methoxymethyl-tetrafluorobenzyl tetramethyl-cyclopropanecarboxylate (K-3050) with or without a synergist were tested by the 25 m3 semi-field test method. One strain (SS) was the most susceptible with KT50 values of about < 30 minutes for all mosquito coils, while the other three strains (BS, A and B) were found to be around 10 to 20 times more tolerant to pyrethroids than the SS strain. A similar tendency for the pyrethroid susceptibility of the four strains was obtained with tests by topical application method. In field efficacy tests, mosquito coils with d, d-T-prallethrin 0.20% plus N-(2-ethylhexyl)bicycle-[2,2,1]- hept-5- ene-2,3-dicarboxyimide as a synergist exhibited a repellent effect of about 85%, while those with K-3050 0.10% plus the synergist exhibited a greater repellent effect of about 90%. In contrast, the repellent effect of commercial dl, d-T80-allethrin 0.20% coils was as low as about 50%. The d, d-T-prallethrin and K-3050 coils with the synergist were confirmed to be highly effective in repelling Ae. aegypti.

Lack of insecticidal effect of mosquito coils containing either metofluthrin or esbiothrin on Anopheles gambiae sensu lato mosquitoes.

Use of mosquito coils for personal protection against malaria and mosquito nuisance is advocated under mosquito and malaria control programmes. We performed field studies of mosquito coils containing either metofluthrin or esbiothrin in experimental huts situated in Kamhororo village, Gokwe district, Zimbabwe. All tests were performed on 3-5 day old reared female Anopheles gambiae sensu lato mosquitoes. The burning times were 9hr 20min for mosquito coils containing metofluthrin and 8 hr for those containing esbiothrin and the results were significantly different (p = <0.001). The mean knock down rate for mosquito coils containing metofluthrin was 90% and that for esbiothrin was 73.3% and the results were significantly different (p = 0.00). Mosquito coils containing metofluthrin had a mean repellence of 92.7% as compared to 85.4% for esbiothrin and the results were not significantly different (p=0.27). The protection time as required by EPA (1999) was 6 hr for mosquito coils containing metofluthrin and 5 hr for those containing esbiothrin. The mean insecticidal effect of mosquito coils containing metofluthrin was 84% as compared to 83% for those containing esbiothrin and the results were not significantly different (p = 0.56). Both mosquito formulations could not be classified as having insecticidal effect since none of them met the 95% mortality rate criteria.

Influence of pyrethroids and piperonyl butoxide on histamine release from isolated rat mast cells.

OBJECTIVE AND DESIGN: Pyrethroids are insecticides with low acute toxicity in mammals but their world-wide use for domestic and occupational purposes has caused concern about the risks of long-term exposure. The mammalian toxicity of pyrethroids is related to disturbances of membrane function in neuronal tissues whereas their influence on nonneuronal tissues is poorly understood. Recently, selected pyrethroids were shown to affect the function of rat synaptosomal and leukocyte membranes similarly. The present investigation explores to what extent their influence on the function of intact cells, i. e. isolated rat mast cells, correlates with these membrane interactions. MATERIALS AND TREATMENT: Permethrin and the more water soluble esbiol (S-bioallethrin), both type I pyrethroids, and cyfluthrin, type II, used alone and together with the enhancing substance piperonyl butoxide (PBO) at concentration ratios of 1:5 and 1:10, were tested for influence on histamine release induced by compound 48/80 without and with calcium. RESULTS: Permethrin (5-10 microM) caused a 10-25 % inhibition of the histamine release in the absence of calcium but did not affect the response with calcium present and had no interaction with PBO. Esbiol (10 microM) was an effective inhibitor on its own, with 70 and 45% inhibition in the absence and presence of calcium, respectively, and caused virtually complete inhibition in a synergistic interaction with PBO. The effect of esbiol could partly be ascribed to inhibition of oxidative energy production. Cyfluthrin was inactive at concentrations up to 10 microM. PBO alone (50 microM) caused some inhibition, in particular in the absence of calcium (ca. 25 %). CONCLUSIONS: The results relating to mast cell histamine release reveal both similarities and differences with the influence of the pyrethroids on cell membrane activities. They indicate that not solely membrane interactions but also additional or alternative targets are involved in the effects of pyrethroids on mammalian tissues. Moreover, the pronounced effects of a brief cell exposure suggest that long-term exposure can be hazardous.

Vector control in leishmaniasis.

Indoor residual spraying is a simple and cost effective method of controlling endophilic vectors and DDT remains the insecticide of choice for the control of leishmaniasis. However resistance to insecticide is likely to become more widespread in the population especially in those areas in which insecticide has been used for years. In this context use of slow release emulsified suspension (SRES) may be the best substitute. In this review spraying frequencies of DDT and new schedule of spray have been discussed. Role of biological control and environment management in the control of leishmaniasis has been emphasized. Allethrin (coil) 0.1 and 1.6 per cent prallethrin (liquid) have been found to be effective repellents against Phlebotomus argentipes, the vector of Indian kalaazar. Insecticide impregnated bednets is another area which requires further research on priority basis for the control of leishmaniasis. Role of satellite remote sensing for early prediction of disease by identifying the sandflygenic conditions cannot be undermined. In future synthetic pheromons can be exploited in the control of leishmaniasis.

[Effect of S-bioallethrin on human lymphocyte].

OBJECTIVE: To study the effect of the S-bioallethrin on human lymphocytes by microarray technique. METHODS: The changes of normal human lymphocytes treated with S-bioallethrin were examined with light microscope, flow cytometry, electron microscope, DNA ladder and microarray techniques. RESULTS: Morphological study showed that the lymphocytes underwent apoptosis after S-bioallethrin exposure, which as further confirmed by the expression changes of 346 genes. CONCLUSION: S-bioallethrin can induce apoptosis of normal human lymphocytes and changes in their gene expression profiles.

Ultra low volume aerosol application of deltacide (deltamethrin 0.5% w/v, S-bioallethrin 0.71% w/v & piperonyl butoxide 8.9% w/v) against mosquitoes.

BACKGROUND & OBJECTIVE: Insecticide in the form of space spray as an ultra low volume (ULV) aerosol are used during epidemics of vector borne diseases. Deltacide, a formulation comprising of three chemicals viz., deltamethrin 0.5 per cent w/v, S-bio-allethrin 0.71 per cent w/v and piperonyl butoxide 8.9 per cent w/v is suitable for ULV application. As this combination is found to be effective in preventing resistance development tackling the population, which had already developed resistance and cause immediate mortality, its synergistic effect was tested in Peet Grady chamber, against three species of mosquitoes, viz., Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus. METHODS: Blood fed females were exposed to ULV application of deltacide in a Peet Grady chamber at four dosages viz., 0.005, 0.01, 0.02 and 0.04 ml/m2 and examined for knockdown activity at 10 min interval for 60 min. Thereafter, the mosquitoes were removed from the chamber and maintained in another room having controlled temperature (28+/-2 degrees C) and humidity (60-75%) and observed for recovery, if any, and the per cent knockdown was calculated. Mortality rate after 24 h of holding period was also determined from moribund and dead adults. RESULTS: Pairwise comparison showed that the effect of deltacide spray varied significantly (P<0.001) among the three species tested. The effectiveness was significantly higher in Ae. aegypti, when compared with that of Cx. quiquefasciatus (P<0.001) and An. stephensi (P<0.05). However, there was no significant difference in the efficacy of deltacide between Cx. quiquefasciatus and An. stephensi. All species of mosquitoes became inactive i.e., knocked down completely within 60 min of exposure at all the dosages tested and mortality observed was 100 per cent after 24 h of exposure. INTERPRETATION & CONCLUSION: Deltacide when tested in the form of ULV cold aerosol, the dosage 0.01 ml/m2 was effective against both Ae. aegypti, and An. stephensi, and 0.02 ml/m2 against Cx. quiquefasciatus, causing 100 per cent mortality. The efficacy of ULV application of deltacide against vector mosquitoes needs to be assessed under field conditions.

Efficacy of thermal fog application of deltacide, a synergized mixture of pyrethroids, against Aedes aegypti, the vector of dengue.

We evaluated the efficacy of indoor and peridomestic thermal fog applications of deltacide, a synergized mixture of pyrethroids (S-bioallethrin 0.7% w/v, deltamethrin 0.5% w/v and piperonyl butoxide 8.9% w/v) against adult populations of Aedes aegypti in Chennai, Tamil Nadu, India. We bioassayed adult caged mosquitoes, counted indoor resting and human landing adult mosquitoes and assessed the percentage of potential breeding sites with Aedes larvae. The bioassay mortalities indicated that the knockdown and killing effect was greater when fogging was applied inside houses rather than around them. Peridomestic thermal fogging reduced the resting and biting populations by 76% and 40%, respectively for the 3 days after treatment, whereas indoor fogging suppressed adult populations for 5 days.

Influence of pyrethroids and piperonyl butoxide on the Ca(2+)-ATPase activity of rat brain synaptosomes and leukocyte membranes.

Pyrethroids are widely used insecticides of low acute toxicity in mammals but the consequences of long-term exposure are of concern. Their insecticidal action is related to neurotoxicity and, in addition, there are indications of mammalian immunotoxicity. In order to clarify structure-activity relationships of the membrane interactions of pyrethroids, the present study compared the influence of selected pyrethroids, i.e. permethrin and the more water soluble esbiol (S-bioallethrin), both type I, and cyfluthrin, type II, on the Ca(2+)-ATPase activity of rat brain synaptosomes and peritoneal leukocyte membranes. The pyrethroids were tested alone as well as mixed with the enhancing substance piperonyl butoxide (PBO) at concentration ratios of 1:5 and 1:10. At the highest concentration tested, permethrin (10 microM) alone inhibited the ATPase activity of leukocyte membranes by 20%, whereas the synaptosomes were affected less. Esbiol and cyfluthrin alone did not affect either membrane preparation significantly, whereas PBO (50 microM) alone caused 10-15% inhibition. Mixtures of either pyrethroid with PBO inhibited the ATPase activity of both types of membranes (up to 40% inhibition) in a synergistic manner, which always tended to be supra-additive. With esbiol a true potentiation took place. The synergistic interaction between pyrethroid and PBO was most apparent with mixtures of a concentration ratio of 1:5. The ATPase activity of leukocyte membranes tended to be more susceptible to inhibition than that of synaptosomes. The results are in accordance with the assumption that the mammalian toxicity of pyrethroids can be ascribed to a general disturbance of cell membrane function in neuronal tissue. The results indicate that it may also be the case in the immune apparatus.

Metofluthrin: a potent new synthetic pyrethroid with high vapor activity against mosquitoes.

(1R)-trans-Norchrysanthemic acid fluorobenzyl esters are synthesized and their structure-activity relationships are discussed. These esters show outstanding insecticidal activity against mosquitoes. In particular, the 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl analog (metofluthrin) exhibits the highest potency, being approximately forty times as potent as d-allethrin in a mosquito coil formulation when tested against southern house mosquitoes (Culex quinquefasciatus). Metofluthrin also exhibits a significant vapor action at room temperature.

Mammalian voltage-gated calcium channels are potently blocked by the pyrethroid insecticide allethrin.

Pyrethroids are commonly used insecticides for both household and agricultural applications. It is generally reported that voltage-gated sodium channels are the primary target for toxicity of these chemicals to humans. The phylogenetic and structural relatedness between sodium channels and voltage-gated calcium (Ca) channels prompted us to examine the effects of the type 1 pyrethroid allethrin on the three major classes of mammalian calcium channels exogenously expressed in human embryonic kidney 293 cells. We report that all classes of mammalian calcium channels are targets for allethrin at concentrations very similar to those reported for interaction with sodium channels. Allethrin caused blockade with IC(50) values of 7.0 microM for T-type alpha(1G) (Ca(v)3.1), 6.8 microM for L-type alpha(1C) (Ca(v)1.2), and 6.7 microM for P/Q-type alpha(1A) (Ca(v)2.1) channels. Mechanistically, the blockade of calcium channels was found to be significantly different than the prolonged opening of mammalian sodium channels caused by pyrethroids. In all calcium channel subtypes tested, allethrin caused a significant acceleration of the inactivation kinetics and a hyperpolarizing shift in the voltage dependence of inactivation. The high-voltage-activated P/Q- and L-type channels showed a frequency of stimulation-dependent increase in block by allethrin, whereas the low-voltage-activated alpha(1G) subtype did not. Allethrin did not significantly modify the deactivation kinetics or current-voltage relationships of any of the calcium channel types. Our study indicates that calcium channels are another primary target for allethrin and suggests that blockade of different types of calcium channels may underlie some of the chronic effects of low-level pyrethroid poisoning.