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Deltamethrin-induced oxidative stress and mitochondrial caspase-dependent signaling pathways in murine splenocytes.
Environ Toxicol. 2016 Jul; 31(7):808-19.ET

Abstract

Deltamethrin (DLM) is a well-known pyrethroid insecticide used extensively in pest control. Exposure to DLM has been demonstrated to cause apoptosis in various cells. However, the immunotoxic effects of DLM on mammalian system and its mechanism is still an open question to be explored. To explore these effects, this study has been designed to first observe the interactions of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has strong binding affinity toward the CD45 and CD28 receptors. In vitro study revealed that DLM induces apoptosis in murine splenocytes in a concentration-dependent manner. The earliest markers of apoptosis such as enhanced reactive oxygen species and caspase 3 activation are evident as early as 1 h by 25 and 50 µM DLM. Western blot analysis demonstrated that p38 MAP kinase and Bax expression is increased in a concentration-dependent manner, whereas Bcl 2 expression is significantly reduced after 3 h of DLM treatment. Glutathione depletion has been also observed at 3 and 6 h by 25 and 50 µM concentration of DLM. Flow cytometry results imply that the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. N-acetyl cysteine effectively reduces the percentage of apoptotic cells, which is increased by DLM. In contrast, buthionine sulfoxamine causes an elevation in the percentage of apoptotic cells. Phenotyping data imply the effect of DLM toxicity in murine splenocytes. In brief, the study demonstrates that DLM causes apoptosis through its interaction with CD45 and CD28 receptors, leading to oxidative stress and activation of the mitochondrial caspase-dependent pathways which ultimately affects the immune functions. This study provides mechanistic information by which DLM causes toxicity in murine splenocytes. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 808-819, 2016.

Authors+Show Affiliations

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Harayana-136119, India.Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25534813

Citation

Kumar, Anoop, et al. "Deltamethrin-induced Oxidative Stress and Mitochondrial Caspase-dependent Signaling Pathways in Murine Splenocytes." Environmental Toxicology, vol. 31, no. 7, 2016, pp. 808-19.
Kumar A, Sasmal D, Bhaskar A, et al. Deltamethrin-induced oxidative stress and mitochondrial caspase-dependent signaling pathways in murine splenocytes. Environ Toxicol. 2016;31(7):808-19.
Kumar, A., Sasmal, D., Bhaskar, A., Mukhopadhyay, K., Thakur, A., & Sharma, N. (2016). Deltamethrin-induced oxidative stress and mitochondrial caspase-dependent signaling pathways in murine splenocytes. Environmental Toxicology, 31(7), 808-19. https://doi.org/10.1002/tox.22091
Kumar A, et al. Deltamethrin-induced Oxidative Stress and Mitochondrial Caspase-dependent Signaling Pathways in Murine Splenocytes. Environ Toxicol. 2016;31(7):808-19. PubMed PMID: 25534813.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deltamethrin-induced oxidative stress and mitochondrial caspase-dependent signaling pathways in murine splenocytes. AU - Kumar,Anoop, AU - Sasmal,D, AU - Bhaskar,Amand, AU - Mukhopadhyay,Kunal, AU - Thakur,Aman, AU - Sharma,Neelima, Y1 - 2014/12/23/ PY - 2014/06/08/received PY - 2014/11/25/revised PY - 2014/12/01/accepted PY - 2014/12/24/entrez PY - 2014/12/24/pubmed PY - 2017/3/7/medline KW - Bax KW - Bcl-2 KW - apoptosis KW - caspase-3 KW - deltamethrin KW - oxidative stress SP - 808 EP - 19 JF - Environmental toxicology JO - Environ Toxicol VL - 31 IS - 7 N2 - Deltamethrin (DLM) is a well-known pyrethroid insecticide used extensively in pest control. Exposure to DLM has been demonstrated to cause apoptosis in various cells. However, the immunotoxic effects of DLM on mammalian system and its mechanism is still an open question to be explored. To explore these effects, this study has been designed to first observe the interactions of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has strong binding affinity toward the CD45 and CD28 receptors. In vitro study revealed that DLM induces apoptosis in murine splenocytes in a concentration-dependent manner. The earliest markers of apoptosis such as enhanced reactive oxygen species and caspase 3 activation are evident as early as 1 h by 25 and 50 µM DLM. Western blot analysis demonstrated that p38 MAP kinase and Bax expression is increased in a concentration-dependent manner, whereas Bcl 2 expression is significantly reduced after 3 h of DLM treatment. Glutathione depletion has been also observed at 3 and 6 h by 25 and 50 µM concentration of DLM. Flow cytometry results imply that the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. N-acetyl cysteine effectively reduces the percentage of apoptotic cells, which is increased by DLM. In contrast, buthionine sulfoxamine causes an elevation in the percentage of apoptotic cells. Phenotyping data imply the effect of DLM toxicity in murine splenocytes. In brief, the study demonstrates that DLM causes apoptosis through its interaction with CD45 and CD28 receptors, leading to oxidative stress and activation of the mitochondrial caspase-dependent pathways which ultimately affects the immune functions. This study provides mechanistic information by which DLM causes toxicity in murine splenocytes. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 808-819, 2016. SN - 1522-7278 UR - https://www.unboundmedicine.com/medline/citation/25534813/Deltamethrin_induced_oxidative_stress_and_mitochondrial_caspase_dependent_signaling_pathways_in_murine_splenocytes_ L2 - https://doi.org/10.1002/tox.22091 DB - PRIME DP - Unbound Medicine ER -