Arif Ahmed Pandit https://orcid.org/0000-0001-7468-0414 R S Sethi http://orcid.org/0000-0003-0416-8946


With Indian pesticide industry touching new heights each year in terms of production and sale, its ill effects on health cannot just be ignored. Humans, as well as animals, are under the constant threat of being exposed to environmental pollutants like endotoxins and pesticides which are present ubiquitously in our surroundings. Phenylpyrazoles like fipronil were introduced into the Indian market with an aim to oversee the menace of insecticide resistance and public health hazards experienced with more commonly used pesticide but its adverse effects on the pulmonary system are now being reported globally. We reported first data that the Planar cell Polarity (PCP) pathway was the top dysregulated pathway during fipronil induced lung damage. In order to further elucidate the underlying molecular mechanisms, we analysed the data generated by gene expression
profiling in lung tissues using biocomputational approaches. We found Eicosanoid signalling as one of the top enriched pathways dysregulated during fipronil and or endotoxin-induced lung inflammation. Global view of genes showed Pla2g5 as top differentially expressed gene with 1.6, 3.9, 1.2, 3.1 and 4.3-folds expression in lipopolysaccharide (LPS), high dose of fipronil (9.5mg/kg) alone or in combination with LPS and low dose of fipronil (4.75 mg/kg) alone or in combination with LPS, respectively which was validated using qPCR and immunohistochemistry. The data suggest a role Pla2g5 to activate eicosanoid signalling in fipronil and or LPS induced lung inflammation in mice.


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Eicosanoid, Fipronil, Immunohistochemistry, LPS, Pla2g5, qPCR

Abhilash, P. C. and N. Singh. (2009). Pesticide use and application: An Indian scenario. Journal of Hazardous Materials, 165(1–3): 1-12. https://doi.org/10.1016/j.jhazmat.2008.10.061.
Arif Ahmad Pandit, C. S. M., Ramneek And R.S. Sethi. (2018). Fipronil Induced Pulmonary Expression of Vcam-1 In Mice. Asian Journal of Microbiology, Biotechnology & Environmental Sciences Paper 20(Dec. Suppl. 2): 253-256.
Back, M. (2007). Leukotriene receptors: crucial components in vascular inflammation. ScientificWorldJournal. 7: 1422-1439. 10.1100/tsw.2007.187.
Bickford, J. S., C. Mueller, K. J. Newsom, S. J. Barilovits, D. E. Beachy, J. D. Herlihy, B. Keeler, T. R. Flotte and H. S. Nick. (2013). Effect of allergy and inflammation on eicosanoid gene expression in CFTR deficiency. J Cyst Fibros. 12(3): 258-265. 10.1016/j.jcf.2012.08.014.
Burgermeister, E., U. Pessara, U. Tibes, A. Küster, P. C. Heinrich and W. V. Scheuer. (2000). Inhibition of cytosolic phospholipase A2 attenuates activation of mitogen-activated protein kinases in human monocytic cells. European Journal of Pharmacology. 388(3): 195-208.
Burke, J. E. and E. A. Dennis. (2009). Phospholipase A(2) structure/function, mechanism, and signaling. Journal of Lipid Research. 50(Suppl): S237-S242. 10.1194/jlr.R800033-JLR200.
Burr, G. O. and M. M. Burr. (1930). On the nature and role of the fatty acids essential in nutrition. Journal of Biological Chemistry. 86(2): 587-621.
Duquenne, P., G. Marchand and C. Duchaine. (2013). Measurement of endotoxins in bioaerosols at workplace: a critical review of literature and a standardization issue. Ann Occup Hyg. 57(2): 137-172. 10.1093/annhyg/mes051.
Giannattasio, G., D. Fujioka, W. Xing, H. R. Katz, J. A. Boyce and B. Balestrieri. (2010). Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function. J Immunol. 185(7): 4430-4438. 10.4049/jimmunol.1001384.
Gupta, P. K. (2004). Pesticide exposure--Indian scene. Toxicology. 198(1-3): 83-90. 10.1016/j.tox.2004.01.021.
Hainzl, D. and J. E. Casida. (1996). Fipronil insecticide: novel photochemical desulfinylation with retention of neurotoxicity. Proc Natl Acad Sci U S A. 93(23): 12764-12767.
Harizi, H., J. B. Corcuff and N. Gualde. (2008). Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol Med. 14(10): 461-469. 10.1016/j.molmed.2008.08.005.
Hossard, L., A. Philibert, M. Bertrand, C. Colnenne-David, P. Debaeke, N. Munier-Jolain, M. H. Jeuffroy, G. Richard and D. Makowski. (2014). Effects of halving pesticide use on wheat production. Scientific Reports. 4: 4405. 10.1038/srep04405https://www.nature.com/articles/srep04405#supplementary-information.
Kannan, K., S. Tanabe and R. Tatsukawa. (1995). Geographical distribution and accumulation features of organochlorine residues in fish in tropical Asia and Oceania. Environ Sci Technol. 29(10): 2673-2683. 10.1021/es00010a032.
Kidd, H. and D. R. James (1991). The agrochemicals handbook.
Kikawada, E., J. V. Bonventre and J. P. Arm. (2007). Group V secretory PLA(2) regulates TLR2-dependent eicosanoid generation in mouse mast cells through amplification of ERK and cPLA(2)? activation. Blood. 110(2): 561-567. 10.1182/blood-2006-10-052258.
Kim, D. K., T. Fukuda, B. T. Thompson, B. Cockrill, C. Hales and J. V. Bonventre. (1995). Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome. Am J Physiol. 269(1 Pt 1): L109-118.
Liu, D., P. Wang, W. Zhu, X. Gu, W. Zhou and Z. Zhou. (2008). Enantioselective degradation of fipronil in Chinese cabbage (Brassica pekinensis). Food Chem. 110(2): 399-405. 10.1016/j.foodchem.2008.02.017.
Merkowsky, K., R. S. Sethi, J. P. S. Gill and B. Singh. (2016). Fipronil induces lung inflammation in vivo and cell death in vitro. Journal of Occupational Medicine and Toxicology (London, England). 11: 10. 10.1186/s12995-016-0102-0.
Ohta, S., M. Imamura, W. Xing, J. A. Boyce and B. Balestrieri. (2013). Group V secretory phospholipase A2 is involved in macrophage activation and is sufficient for macrophage effector functions in allergic pulmonary inflammation. J Immunol. 190(12): 5927-5938. 10.4049/jimmunol.1203202.
Pandit, A. A., S. Choudhary, Ramneek, B. Singh and R. S. Sethi. (2016). Imidacloprid induced histomorphological changes and expression of TLR-4 and TNFalpha in lung. Pestic Biochem Physiol. 131: 9-17. 10.1016/j.pestbp.2016.02.004.
Pandit, A. A., R. K. Gandham, C. S. Mukhopadhyay, R. Verma and R. S. Sethi. (2019). Transcriptome analysis reveals the role of the PCP pathway in fipronil and endotoxin-induced lung damage. Respiratory Research. 20(1): 24. 10.1186/s12931-019-0986-1.
Pandit, A. A., C. S. Mukhopadhyay and R. S. Sethi. (2017). Expression of TLR-9 and IL-1 following Concomitant Exposure to Imidacloprid and Endotoxin. Pesticide Research Journal. 29(2): 243-250.
Ricciotti, E. and G. A. FitzGerald. (2011). Prostaglandins and inflammation. Arteriosclerosis, thrombosis, and vascular biology. 31(5): 986-1000. 10.1161/ATVBAHA.110.207449.
Sandeep, K., C. S. Mukhopadhyay, J. S. Arora and R. S. Sethi. (2016). Indoxacarb interaction alters immunotoxic and genotoxic potential of endotoxin. Journal of pesticide science. 41(3): 65-70. 10.1584/jpestics.D16-012.
Sethi, R. S., R. S. Brar, O. Singh and B. Singh. (2011). Immunolocalization of Pulmonary Intravascular Macrophages, TLR4, TLR9 and IL-8 in Normal and Pasteurella multocida-infected Lungs of Water Buffalo (Bubalus bubalis). Journal of Comparative Pathology. 144(2): 135-144. https://doi.org/10.1016/j.jcpa.2010.08.003.
Sethi, R. S., D. Schneberger, C. Charavaryamath and B. Singh. (2017). Pulmonary innate inflammatory responses to agricultural occupational contaminants. Cell Tissue Res. 367.
Sethi, R. S., D. Schneberger and B. Singh. (2013). Characterization of the lung epithelium of wild-type and TLR9?/? mice after single and repeated exposures to chicken barn air. Experimental and Toxicologic Pathology. 65(4): 357-364. https://doi.org/10.1016/j.etp.2011.11.002.
Subhash, P.S., Chand, P., Pavithra, S., Balaji, S. J., & Pal, S. (2017). Pesticide Use in Indian Agriculture: Trends, Market Structure and Policy Issues.
Tewari, A., R. S. Sethi, H. S. Banga, B. Singh and J. Gill. (2017). Concomitant effect of low dose of lindane and intranasal lipopolysaccharide on respiratory system of mice. Hum Exp Toxicol. 36(11): 1201-1211. 10.1177/0960327116685889.
Tischfield, J. A., Y. R. Xia, D. M. Shih, I. Klisak, J. Chen, S. J. Engle, A. N. Siakotos, M. V. Winstead, J. J. Seilhamer, V. Allamand, G. Gyapay and A. J. Lusis. (1996). Low-molecular-weight, calcium-dependent phospholipase A2 genes are linked and map to homologous chromosome regions in mouse and human. Genomics. 32(3): 328-333. 10.1006/geno.1996.0126.
Tomlin, C. D. (2009). The pesticide manual: a world compendium, British Crop Production Council.
Verma Geetika, Verma Ramneek, Mukhopadhyay CS and Sethi RS. (2016). Acute ethion exposure alters expression of TLR 9 in lungs of mice. Indian Journal of Veterinary Anatomy 28 (1): 40-43.
Verma, G., C. S. Mukhopadhyay, R. Verma, B. Singh and R. S. Sethi. (2018). Long-term exposures to ethion and endotoxin cause lung inflammation and induce genotoxicity in mice. Cell Tissue Res. 10.1007/s00441-018-2912-0.
Yamaguchi, M., S. K. Samuchiwal, O. Quehenberger, J. A. Boyce and B. Balestrieri. (2018). Macrophages regulate lung ILC2 activation via Pla2g5-dependent mechanisms. Mucosal Immunol. 11(3): 615-626. 10.1038/mi.2017.99.
Yamaguchi, Y., K. Fujio, H. Shoda, A. Okamoto, N. H. Tsuno, K. Takahashi and K. Yamamoto. (2007). IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis. J. Immunol. 179(10): 7128-7136.
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Pandit, A. A., & Sethi, R. S. (2019). Pulmonary expression of Pla2g5 during lung damage in mice induced by fipronil and lipopolysaccharide interaction. Journal of Applied and Natural Science, 11(2), 285-290. https://doi.org/10.31018/jans.v11i2.2043
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