piperidines and decamethrin

Deltamethrin (DLM) is a well-known pyrethroid insecticide which is widely used in the agriculture and home pest control due to restriction on the sale of organophosphate. DLM induced apoptosis is well known but its mechanism is still unclear. This study has been designed to find out its mechanism of apoptosis with the help of computational methods along with in vivo methods. The QikProp and ProTox results have shown that DLM has good oral absorption. The docking results reveal that DLM has a strong binding affinity toward the CD4, CD8, CD28 and CD45 receptors. Further, to understand the toxicity of DLM on lymphoid cells, a single dose of DLM (5 mg/kg, oral for seven days) has been administered to male Balb/c mice and cytotoxicity (MTT assay), oxidative stress indicators (glutathione, reactive oxygen species) and apoptotic markers (caspase-3 activity, DNA fragmentation) have been assessed in thymic and splenic single cell suspensions. Lowering of body weight, cellularity and loss in cell viability have been observed in DLM treated mice. The significant increase in ROS and GSH depletion in spleen and thymus, indicate the possible involvement of oxidative stress. The spleen cells appear more susceptible to the adverse effects of DLM than thymus cells. Further, for the amelioration of its effect, two structurally different bioactive herbal extracts, piperine and curcumin have been evaluated and have shown the cytoprotective effect by inhibiting the apoptogenic signaling pathways induced by DLM.

Topics: Alkaloids; Animals; Antioxidants; Apoptosis; Benzodioxoles; Caspase 3; Cell Survival; Curcumin; Cytoprotection; Glutathione; Insecticides; Male; Mice, Inbred BALB C; Molecular Docking Simulation; Nitriles; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Protein Binding; Protein Conformation; Pyrethrins; Reactive Oxygen Species; Receptors, Immunologic; Spleen; Structure-Activity Relationship; Thymus Gland; Time Factors

A new approach employing a combination of pyrethroid and repellent is proposed to improve the protective efficacy of conventional pyrethroid-treated fabrics against mosquito vectors. In this context, the insecticidal and repellent efficacies of commonly used pyrethroids and repellents were evaluated by cone tests and arm-in-cage tests against Stegomyia albopicta (=Aedes albopictus) (Diptera: Culicidae). At concentrations of LD50 (estimated for pyrethroid) or ED50 (estimated for repellent), respectively, the knock-down effects of the pyrethroids or repellents were further compared. The results obtained indicated that deltamethrin and DEET were relatively more effective and thus these were selected for further study. Synergistic interaction was observed between deltamethrin and DEET at the ratios of 5 : 1, 2 : 1, 1 : 1 and 1 : 2 (but not 1 : 5). An optimal mixing ratio of 7 : 5 was then microencapsulated and adhered to fabrics using a fixing agent. Fabrics impregnated by microencapsulated mixtures gained extended washing durability compared with those treated with a conventional dipping method. Results indicated that this approach represents a promising method for the future impregnation of bednet, curtain and combat uniform materials.

Topics: Aedes; Animals; Chromatography, High Pressure Liquid; Clothing; Culicidae; DEET; Drug Compounding; Insect Repellents; Insecticides; Laundering; Mosquito Control; Nitriles; Permethrin; Piperidines; Propionates; Pyrethrins

Deltamethrin (DLM), a well-known pyrethroid insecticide, is a potent immunotoxicant. In rodents, it is primarily characterized by marked thymic apoptosis. Mechanism of DLM induced thymic apoptosis in primary murine thymocytes has been recently explored. Oxidative stress and activation of caspase dependent pathways appear to be involved in the DLM induced thymic injury. Thus, for the amelioration of its effect, this study has been designed to first observe the binding affinity of piperine to immune cell receptors and its protective effects on the DLM induced immunotoxicity under in vitro condition. The docking results demonstrated that piperine has good binding affinity towards CD4 and CD8 receptors. In vitro study results have shown that piperine (1, 10 and 50 μg/ml) increased cell viability in a concentration dependent manner. The early activated markers of apoptosis such as enhanced reactive oxygen species (ROS) and caspase-3 activation by DLM was significantly reduced by piperine treatment. GSH depletion induced by DLM has been also restored by piperine treatment. At 18 h, all concentration of piperine (1, 10 and 50 μg/ml) significantly ameliorated the DLM induced apoptosis. Further, DLM induced phenotypic changes were mitigated by the piperine. In addition, piperine also restored the cytokine levels, which were suppressed by DLM treatment. These findings strongly indicate the anti-oxidative, anti-apoptotic and chemo-protective ability of piperine in the DLM induced thymic apoptosis.

Topics: Alkaloids; Animals; Antioxidants; Apoptosis; Benzodioxoles; Caspase 3; CD4 Antigens; Cell Survival; Glutathione; Immunologic Factors; Interferon-gamma; Interleukin-2; Interleukin-4; Male; Mice, Inbred BALB C; Molecular Docking Simulation; Nitriles; Piperidines; Polyunsaturated Alkamides; Pyrethrins; Reactive Oxygen Species; Receptors, Antigen, T-Cell; Thymocytes

Deltamethrin (DLM) being a potent immunotoxicant affects both humoral and cell mediated immunity. Thus, for the amelioration of its effects, two different bioactive herbal extracts piperine and curcumin are evaluated and their efficacy has been compared. The docking results demonstrated that curcumin has good binding affinity towards CD28 and CD45 receptors as compared to piperine but in vitro studies revealed that piperine is more effective. DLM induced apoptotic markers such as oxidative stress and caspase 3 have been attenuated more significantly by piperine as compared to curcumin. Phenotypic and cytokine changes have also been mitigated best with piperine. Thus, these findings strongly demonstrate that piperine displays the more anti-oxidative, anti-apoptotic and chemo-protective properties in the DLM induced splenic apoptosis as compared to curcumin. So, piperine can be considered the drug of choice under immunocompromised conditions.

Topics: Alkaloids; Animals; Apoptosis; Benzodioxoles; CD28 Antigens; Curcumin; Humans; Immunity; Leukocyte Common Antigens; Male; Mice; Mice, Inbred BALB C; Nitriles; Piperidines; Polyunsaturated Alkamides; Pyrethrins; Spleen

The spread of resistance to pyrethroids in the major Afrotropical malaria vectors Anopheles gambiae s.s. necessitates the development of new strategies to control resistant mosquito populations. To test the efficacy of nets treated with repellent and insecticide against susceptible and insecticide-resistant An. gambiae mosquito populations, we impregnated mosquito bed nets with an insect repellent mixed with a low dose of organophosphorous insecticide and tested them in a rice-growing area near Bobo-Dioulasso, Burkina Faso. During the first 2 weeks posttreatment, the mixture was as effective as deltamethrin alone and was more effective at killing An. gambiae that carried knockdown resistance (kdr) or insensitive acetylcholinesterase resistance (Ace1R) genes. The mixture seemed to not kill more susceptible genotypes for the kdr or Ace1R alleles. Mixing repellents and organophosphates on bed nets could be used to control insecticide-resistant malaria vectors if residual activity of the mixture is extended and safety is verified.

Topics: Acetylcholinesterase; Alleles; Animals; Anopheles; Burkina Faso; Cholinesterase Inhibitors; DEET; Female; Genes, Insect; Humans; Insect Repellents; Insect Vectors; Insecticide Resistance; Insecticides; Malaria; Male; Mosquito Control; Nitriles; Organothiophosphorus Compounds; Piperidines; Pyrethrins