Upregulation Of Eicosanoid Signalling In Lung Following Fipronil And Endotoxin Interaction

Abstract

It is estimated that nearly 1.8 billion people worldwide use pesticides to minimize the crop damage in efforts to increase food production to feed the growing world population. Exposures to lower concentartion of various pesticides such as fipronil and phenylpyrazole can result in fatal poisonings as well as airway inflammation. Inhalation of endotoxins, which are frequently present in the agricultural buildings, also induces lung inflammation. Animals exposed to both fipronil and endotoxin may demonstrate enhanced lung inflammation. There, however, are limited data available on the molecular mechanisms underlying the toxicity induced by fipronil alone or in combination with endotoxin. Hence, we employed a comprehensive microarray approach in a mouse model to identify the molecular mechanism involved in the lung inflammation by exposing the mice to fipronil (1/20th of LD50/d orally for 90 d) followed by intranasal E. coli LPS (80μg/mouse) or normal saline (N=10 each). Fipronil with or without LPS significantly (p<0.05) increased the total histopathological score suggesting lung damage. Ingenuity Pathway Analysis (IPA) software analysis predicted eicosanoid signalling among the top 5 canonical pathways involved in airway inflammation. Eicosanoid signalling plays important role in pulmonary inflammation and immune response via cytokine production, cell proliferation, antibody formation and antigen presentation. Fipronil alone caused 3‐fold increase in Phospholipase A2G5 (PLA2G5), which hydrolyses the membrane phospholipids to generate various eicosanoids. PLA2G5 showed 1.63 and 4.34 fold increase following exposure to endotoxin alone or in combination with fipronil, respectively. RT‐qPCR and immunohistochemistry analysis validated the microarray data for the PLA2G5. The data taken together indicate up‐regulation of functionally relevant PLA2G5 during fipronil or/and endotoxin induced lung inflammation, which may also play a role in lung inflammation associated with fipronil exposure.Support or Funding InformationGADVASU, LudhianaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.