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Deltamethrin induced an apoptogenic signalling pathway in murine thymocytes : exploring the molecular mechanism.
J Appl Toxicol. 2014 Dec; 34(12):1303-10.JA

Abstract

Deltamethrin (DLM) is a well-known pyrethroid insecticide; however, the immunotoxic effects of DLM on the mammalian system and its mechanism is still unclear. This study has been designed to first observe the binding affinity of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has a strong binding affinity towards the CD4 and CD8 receptors. DLM induces apoptosis in murine thymocytes in a concentration-dependent manner. The ear\ly markers of apoptosis such as enhanced reactive oxygen species (ROS) and caspase-3 activation are evident as early as 1 h by 25 and 50 μM DLM. Glutathione (GSH) depletion has also been observed at 1 h by 50 μM DLM concentration. In cell-cycle studies using flow cytometry, the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. The Annexin V binding assay measures the effect of DLM on apoptotic and necrotic cells. The apoptotic cells raised from 18.6% to 35.21% (10-50 μM DLM) at 18 h. N-acetyl cysteine (NAC) effectively reduced the percentage of apoptotic cells which is increased by DLM. In contrast, buthionine sulfoximine (BSO) caused an elevation in the percentage of apoptotic cells. These results demonstrate that caspase activation, ROS activation and GSH act as critical mediators in a DLM-induced apoptogenic signalling pathway in murine thymocytes. In the presence of caspase inhibitor, the percentage of apoptotic cells is partially decreased. Thus, there may be the possibility of some other caspase-independent pathways in DLM-induced apoptosis.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, 835215, Jharkhand, India.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24217896

Citation

Kumar, Anoop, et al. "Deltamethrin Induced an Apoptogenic Signalling Pathway in Murine Thymocytes : Exploring the Molecular Mechanism." Journal of Applied Toxicology : JAT, vol. 34, no. 12, 2014, pp. 1303-10.
Kumar A, Sasmal D, Sharma N. Deltamethrin induced an apoptogenic signalling pathway in murine thymocytes : exploring the molecular mechanism. J Appl Toxicol. 2014;34(12):1303-10.
Kumar, A., Sasmal, D., & Sharma, N. (2014). Deltamethrin induced an apoptogenic signalling pathway in murine thymocytes : exploring the molecular mechanism. Journal of Applied Toxicology : JAT, 34(12), 1303-10. https://doi.org/10.1002/jat.2948
Kumar A, Sasmal D, Sharma N. Deltamethrin Induced an Apoptogenic Signalling Pathway in Murine Thymocytes : Exploring the Molecular Mechanism. J Appl Toxicol. 2014;34(12):1303-10. PubMed PMID: 24217896.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deltamethrin induced an apoptogenic signalling pathway in murine thymocytes : exploring the molecular mechanism. AU - Kumar,Anoop, AU - Sasmal,D, AU - Sharma,Neelima, Y1 - 2013/11/12/ PY - 2013/08/08/received PY - 2013/09/13/revised PY - 2013/09/18/accepted PY - 2013/11/13/entrez PY - 2013/11/13/pubmed PY - 2015/6/24/medline KW - apoptosis KW - caspase-3 KW - deltamethrin KW - murine thymocytes KW - oxidative stress SP - 1303 EP - 10 JF - Journal of applied toxicology : JAT JO - J Appl Toxicol VL - 34 IS - 12 N2 - Deltamethrin (DLM) is a well-known pyrethroid insecticide; however, the immunotoxic effects of DLM on the mammalian system and its mechanism is still unclear. This study has been designed to first observe the binding affinity of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has a strong binding affinity towards the CD4 and CD8 receptors. DLM induces apoptosis in murine thymocytes in a concentration-dependent manner. The ear\ly markers of apoptosis such as enhanced reactive oxygen species (ROS) and caspase-3 activation are evident as early as 1 h by 25 and 50 μM DLM. Glutathione (GSH) depletion has also been observed at 1 h by 50 μM DLM concentration. In cell-cycle studies using flow cytometry, the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. The Annexin V binding assay measures the effect of DLM on apoptotic and necrotic cells. The apoptotic cells raised from 18.6% to 35.21% (10-50 μM DLM) at 18 h. N-acetyl cysteine (NAC) effectively reduced the percentage of apoptotic cells which is increased by DLM. In contrast, buthionine sulfoximine (BSO) caused an elevation in the percentage of apoptotic cells. These results demonstrate that caspase activation, ROS activation and GSH act as critical mediators in a DLM-induced apoptogenic signalling pathway in murine thymocytes. In the presence of caspase inhibitor, the percentage of apoptotic cells is partially decreased. Thus, there may be the possibility of some other caspase-independent pathways in DLM-induced apoptosis. SN - 1099-1263 UR - https://www.unboundmedicine.com/medline/citation/24217896/Deltamethrin_induced_an_apoptogenic_signalling_pathway_in_murine_thymocytes_:_exploring_the_molecular_mechanism_ L2 - https://doi.org/10.1002/jat.2948 DB - PRIME DP - Unbound Medicine ER -