Chronic exposure to endosulfan induces inflammation in murine colon via β-catenin expression and IL-6 production

Abstract

Endosulfan (ENDO) is a widely used organochlorine (OC) pesticide and persistent organo-pollutant. Epidemiological studies have shown that high levels of OC exposure were related to colorectal cancer (CRC) incidence. The objectives of the present study were to evaluate histological changes in the colon, as well as in in situ expression of b-catenin and P-selectin, and serum levels of select pro-inflammatory cytokines in mice administered ENDO; there is a relationship between increased serum IL-6 and P-selectin levels in CRC patients and aberrant b-catenin signaling is important in initiation/maintenance of most CRCs. Mice were exposed to ENDO (at dose < LD 50 ) orally once a week for up to 24 weeks, and monitored (inclusive) for a total of 42 weeks. The experiment was comprised of three groups, one that did not receive ENDO (olive oil vehicle), one administered 2 mg ENDO/kg/week and a positive control (for induction of CRC) given a weekly 20 mg 1,2-dimethylhydrazine (DMH)/kg injection. The results indicated that oral administration of ENDO provoked moderate inflammation starting at six weeks, and severe colonic inflammation with an appearance of dysplastic formations (aberrant crypts) in mice treated with ENDO (or DMH) for 12 weeks or longer. Serum IL-6 levels significantly increased starting at six weeks and rose to a peak of 15-fold higher than in controls at 42 weeks; TNFa levels likewise significantly increased, with a later peak (%four-fold higher than controls) at 30-42 weeks. Immunohistochemical analysis of the colon also showed that expression of b-catenin and P-selectin increased with length of exposure to ENDO. Taken together, the results indicate that continued repeated oral exposure to ENDO induces increased expression of b-catenin and P-selectin, inflammation in the colon, and, ultimately, local tissue dysplasia. ARTICLE HISTORY

Associations of Dietary Exposure to Organochlorine Pesticides from Plant-origin Foods with Lipid Metabolism and Inflammation in Childbearing-age Women: A Multiple Follow-up Study in North China

“…Exposure to endosulfans and dieldrin can increase the expression levels of the pro-in ammatory factors IL-6, IL-8, IL-1β, and TNF-α, as evidenced in molecular studies [13,46]. Female mice and rats had increased levels of pro-in ammatory cytokines when exposed to doses ranging from 2-50 mg/kg of endosulfans [18,47], which is consistent with our results. However, no signi cant associations were found between serum dieldrin, endosulfan-α, and endosulfan-β and cytokines (i.e., IL-2, IL-4, IL-6, and IL-10) in preterm birth cases in a case-control study in India, and only endosulfan-β was positively correlated with IL-2 in the controls [48].…”

Effects of endosulfan isomers on cytokine and nitric oxide production by differentially activated RAW 264.7 cells

“…In vivo studies have shown that endosulfan exposure can increase the level or activity of a number of inflammatory factors in animals. For example, inducible nitric oxide synthase was elevated by endosulfan exposure in rat and frog tissues [ [12] , [24] , [25] ], and increased expression of inflammatory cytokines, including TNF, IL-1 and IL-6, have been reported in rats and mice [ [26] , [27] , [28] ]. In many tissues, macrophages are a principle source of inflammatory cytokines and NO.…”

Impact of polypropylene microplastics and chemical pollutants on European sea bass (Dicentrarchus labrax) gut microbiota and health

“…This result agrees with the tendency of fish intestine to present a wider lamina propria. The effects of certain contaminants on gut cytokines have been described in mammals, with an increase in proinflammatory cytokines, including il-6 or tnf-α associated with CPF exposure (Li et al, 2019) or organochlorine pesticides (Téllez-Bañuelos et al, 2016). Conversely, virgin MPs and chemical pollutants used singularly did not induce the expression of tested immunity-related cytokines.…”