curcumin and decamethrin

We aimed to prove that oxidative stress is the main mechanism responsible for hippocampal neurotoxicity induced by deltamethrin (DLM). The protective role of curcumin (CMN) and nano-curcumin (NCMN) over this toxicity was studied. The rats were categorized into four groups: control, DLM, CMN and NCMN. The study continued for 30 days. Hippocampus was processed for histological, biochemical and immunohistochemical studies. Caspase-3, glial fibrillar acidic protein (GFAP), acetylcholinesterase (AChE), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were measured for DLM-induced oxidative stress (increased MDA by 354%/decreased GSH by 61%, SOD by 61%, CAT 57%). Oxidative stress induced apoptosis of hippocampal neurons through increasing Nrf2, gamma-glutamyl cysteine synthetase heavy subunit (GCS-HS) and light subunit (GCS-LS) and decreasing AChE. It increases the activity of astrocytes through increasing GFAP. Finally, oxidative stress has a bad impaction on cognitive function. Improvement of oxidative stress was observed with use of CMN and NCMN (decrease of MDA/increase of GSH, SOD, CAT). The level of Nrf2, GCS-HS and GCS-LS decreased, while AChE, GFAP increased. Improvement of cognitive function was observed in both groups. In conclusion, oxidative stress is the common mechanism responsible for DLM-induced hippocampal neurotoxicity. It exerts apoptosis of hippocampal neurons through increasing Nrf2, HS-GCS, LS-GCS and decreasing AChE. In addition, it activates astrocytes through increasing expression of GFAP. The protective role of CMN and CMMN is related to their potent antioxidant effect. Much improvement has been detected with NCMN as compared to CMN.

Topics: Animals; Antioxidants; Apoptosis; Curcumin; Hippocampus; Insecticides; Maze Learning; Nanoparticles; Neurons; Nitriles; Oxidative Stress; Protective Agents; Pyrethrins; Rats; Rats, Wistar

Deltamethrin (DLM) is a synthesized organophosphorus acaricide and bug spray, broadly utilized for veterinary and farming purposes. Although its exposure to humans and animals causes toxicity in the kidney and other primary organs, our objective was to assess the defensive effects of sitagliptin (Sita) and additionally curcumin (Cur) in the DLM-intoxicated rats' kidney. DLM-intoxicated rats revealed a huge increase of various biochemical parameters in serum identified with kidney damage: uric acid, urea, and creatinine. DLM intoxication altogether increased renal lipid peroxidation, and critically restrained antioxidative biomarkers including superoxide dismutase, glutathione, and glutathione peroxidase. Likewise, it increased the tumor necrosis factor-α, interleukin 6 (IL-6) and IL-1β level in serum. Additionally, DLM intoxication diminished the outflow of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in rats. Both Sita and Cur act against DLM-prompted serum along with renal tissue biochemical parameters when utilized alone or in a mix alongside DLM intoxication. Besides this, both Sita and Cur delivered synergetic nephroprotective, antioxidative, and anti-inflammatory impacts. Consequently, it could be presumed that Sita as well as Cur administration can limit the poisonous impacts of DLM by their free radical-scavenging, strong antioxidant, and Nrf2/HO-1 pathway upregulation activity.

Topics: Acaricides; Animals; Biomarkers; Curcumin; Cytokines; Drug Synergism; Heme Oxygenase-1; Hypoglycemic Agents; Inflammation Mediators; Kidney; Male; NF-E2-Related Factor 2; Nitriles; Pyrethrins; Rats; Rats, Wistar; Sitagliptin Phosphate

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

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

Curcumin, a main component of Curcuma Longa Linn, is a plant polyphenol used as an immune-enhancer in the Indian system of traditional medicine. However, its underlying mechanism of immune-protection remains unknown. The present study is designed to delineate the role of curcumin in deltamethrin (DLM)-induced thymocyte apoptosis and altered immune functions. In silico studies revealed that curcumin has a strong binding affinity toward CD4 and CD8 receptors. DLM (25 µM) induces thymocytes apoptosis through oxidative stress and caspase-dependent pathways. Various concentrations of curcumin (1, 10 and 50 µg/ml), when added along with DLM, caused a concentration- and time-related amelioration in apoptogenic signaling pathways induced by DLM. Inhibition of DLM-induced reactive oxygen species production, replenishment of glutathione and suppression of caspase activities by curcumin may thus be responsible for the suppression of downstream cascade of events, i.e. apoptosis, phenotypic changes and altered cytokine release. Thus, this study clearly demonstrates that the mechanism of immunoprotection of curcumin in DLM-induced thymic apoptosis includes inhibition of oxidative stress and caspase-dependent pathways underlying apoptosis.

Topics: Animals; Apoptosis; CD4 Antigens; Cell Survival; Cells, Cultured; Computer Simulation; Curcumin; Dose-Response Relationship, Drug; Immunity, Cellular; Immunomodulation; Male; Mice; Mice, Inbred BALB C; Nitriles; Oxidative Stress; Protein Structure, Secondary; Protein Structure, Tertiary; Pyrethrins; Thymus Gland