Comparison of intestinal toxicity in enhancing intestinal permeability and in causing ROS production of six PPD quinones in Caenorhabditis elegans

Abstract

As the derivatives of p-phenylenediamines (PPDs), PPD quinones (PPDQs) have received increasing attention due to their possible exposure risk. We compared the intestinal toxicity of six PPDQs (6-PPDQ, 77PDQ, CPPDQ, DPPDQ, DTPDQ and IPPDQ) in Caenorhabditis elegans. In the range of 0.01-10 μg/L, only 77PDQ (10 μg/L) moderately induced the lethality. All the examined PPDQs at 0.01-10 μg/L did not affect intestinal morphology. Different from this, exposure to 6-PPDQ (1-10 μg/L), 77PDQ (0.1-10 μg/L), CPPDQ (1-10 μg/L), DPPDQ (1-10 μg/L), DTPDQ (1-10 μg/L), and IPPDQ (10 μg/L) enhanced intestinal permeability to different degrees. Meanwhile, exposure to 6-PPDQ (0.1-10 μg/L), 77PDQ (0.01-10 μg/L), CPPDQ (0.1-10 μg/L), DPPDQ (0.1-10 μg/L), DTPDQ (1-10 μg/L), and IPPDQ (1-10 μg/L) resulted in intestinal reactive oxygen species (ROS) production and activation of both SOD-3::GFP and GST-4::GFP. In 6-PPDQ, 77PDQ, CPPDQ, DPPDQ, DTPDQ, and/or IPPDQ exposed nematodes, the ROS production was strengthened by RNAi of genes (acs-22, erm-1, hmp-2, and pkc-3) governing functional state of intestinal barrier. Additionally, expressions of acs-22, erm-1, hmp-2, and pkc-3 were negatively correlated with intestinal ROS production in nematodes exposed to 6-PPDQ, 77PDQ, CPPDQ, DPPDQ, DTPDQ, and/or IPPDQ. Therefore, exposure to different PPDQs differentially induced the intestinal toxicity on nematodes. Our data highlighted potential exposure risk of PPDQs at low concentrations to organisms by inducing intestinal toxicity.

Keywords: C. elegans; Intestinal toxicity; PPDQs; Toxicity comparison.