Abstract
Organophosphorus pesticides (OPs) can be metabolized to diethyl phosphate (DEP) in the gut environment, which may affect the immune and endocrine systems and the microbiota. Correlations between OPs and diseases have been established by epidemiological studies, mainly based on the contents of their metabolites, including DEP, in the serum or urine. However, the effects of DEP require further study. Therefore, in this study, adult male rats were exposed to 0.08 or 0.13 mg/kg DEP for 20 weeks. Serum levels of hormones, lipids, and inflammatory cytokines as well as gut microbiota were measured. DEP significantly enriched opportunistic pathogens, including Paraprevotella, Parabacteroides, Alloprevotella, and Helicobacter, leading to a decrease in interleukin-6 (IL-6). Exposure to the high dose of DEP enriched the butyrate-producing genera, Alloprevotella and Intestinimonas, leading to an increase in estradiol and a resulting decrease in total triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C); meanwhile, DEP-induced increases in peptide tyrosine‒tyrosine (PYY) and ghrelin were attributed to the enrichment of short-chain fatty acid-producing Clostridium sensu stricto 1 and Lactobacillus. These findings indicate that measuring the effects of DEP is not a proxy for measuring the effects of its parent compounds.
Highlights
Organophosphorus pesticides (OPs) are frequently detected in food [1,2,3], and about 75% of all registered OPs are metabolized in the body into measurable dialkyl phosphate metabolites, such as diethyl phosphate (DEP) [4]
The levels of DEP in this study were based on the molar doses corresponding to the doses of triazophos and chlorpyrifos in our previous studies
Triazophos and chlorpyrifos are pesticides frequently detected in vegetables and fruits, and we evaluated the endocrine-disrupting effects of the two pesticides at the dose of 1/500 LD50
Summary
Organophosphorus pesticides (OPs) are frequently detected in food [1,2,3], and about 75% of all registered OPs are metabolized in the body into measurable dialkyl phosphate metabolites, such as diethyl phosphate (DEP) [4]. The endocrine-disrupting effects of OPs, including chlorpyrifos [13,14,15,16,17,18], diazinon [19,20], malathion [21], triazophos [22], and dimethoate [23], have only been proven in animal studies, which reported a disorder of hormones involved in the hypothalamic-pituitary-adrenal [20], hypothalamic-pituitary-thyroid [14,17,18,19], and hypothalamic-pituitary-gonadal axes [14,15,16,17,21,22,23] All of these OPs metabolize to DEP in vivo; we do not know whether these effects are induced by the parent OPs or the metabolites, especially the non-specific metabolite, DEP.
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