Sub-Chronic Low-Doses of Chlorpyrifos Exposure Alter Short Chain Fatty Acid Levels and Causes Insulin Resistance

Author:

Sakinah Elly Nurus1,Mustika Arifa2,Wibisono Sony2,Zhou Xian3

Affiliation:

1. Airlangga University, University of Jember

2. Airlangga University

3. NICM Health Research Institute, Western Sydney University

Abstract

Abstract Background Indonesia is an agricultural country which has more than 33 million workers in agriculture. Chlorpyrifos is an organophosphate pesticide that is extensively used in agriculture attributed to its broad application on crops. The primary route of human exposure to pesticide residues is through oral ingestion. The specific toxic effect of chlorpyrifos exposure appeared to be associated with dysbiosis, reduced short-chain fatty acid (SCFA), and the incidence of hyperglycemia depending on the dose and duration. This study aims to evaluate the impact of chlorpyrifos exposure on SCFA levels-induced insulin resistance. Methods Thirty Wistar rats were divided into five different time exposure groups [0 days (Control group), 7 days (P1), 14 days (P2), 28 days (P3), and 56 days (P4)]. Chlorpyrifos was given 5 mg/kg BW orally every day. Jejunum villi height was measured to observe the intestinal barrier tight junction, and SCFA was evaluated by GCMS methods. Fasting blood glucose and fasting insulin were measured to calculate Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Results Oral exposure of chlorpyrifos decreased jejunum villi height, total SCFA levels, and increased the fasting blood glucose, the fasting insulin and HOMA-IR levels. P4 group (day 56) was lower jejunum villi height, lower total SCFA level, higher fasting blood glucose, higher fasting insulin and higher HOMA-IR levels than the control group (day 0) at p < 0.05 using ANOVA. Conclusion Sub-chronic low-dose chlorpyrifos exposure (5 mg/kg daily for 56 days) in rats led to significant insulin resistance and reduced SCFA levels. The strong time-effect relationship suggests that negative impact increasing with time and become prominent by day 56. These findings can provide valuable insights to users/farmers regarding the potential limitations on the duration of daily exposure.

Publisher

Research Square Platform LLC

Reference32 articles.

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