title: Deltamethrin-induced oxidative stress and mitochondrial caspase-dependent signaling pathways in murine splenocytes.
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.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.
authors.forename: Anoop
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.
authors.forename: D
authors.initials: D
authors.lastname: Sasmal
authors.affiliation: Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.
authors.forename: Amand
authors.initials: A
authors.lastname: Bhaskar
authors.affiliation: Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.
authors.forename: Kunal
authors.initials: K
authors.lastname: Mukhopadhyay
authors.affiliation: Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Harayana-136119, India.
authors.forename: Aman
authors.initials: A
authors.lastname: Thakur
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.
authors.forename: Neelima
authors.initials: N
authors.lastname: Sharma
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D007107:Immune System / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D062105:Molecular Docking Simulation; D009570:Nitriles / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D011722:Pyrethrins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; D020169:Caspases; D005978:Glutathione; D000111:Acetylcysteine
keywords: Bax; Bcl-2; apoptosis; caspase-3; deltamethrin; oxidative stress