Transgenerational intestinal toxicity of 6-PPD quinone in causing ROS production, enhancement in intestinal permeability and suppression in innate immunity in C. elegans.

Toxicity of 6-PPD quinone (6-PPDQ) on organisms at various aspects has been frequently observed at parental generation (P0-G). In contrast, we know little about its possible transgenerational toxicity and underlying mechanisms. In Caenorhabditis elegans, exposure to 6-PPDQ (0.1-10 μg/L) at P0-G induced transgenerational reactive oxygen species (ROS) production in intestine. Accompanied with this, transgenerational increase in intestinal permeability and decrease in expressions of genes governing intestinal function were observed. Exposure to 6-PPDQ (1 and 10 μg/L) at P0-G caused transgenerational suppression in expressions of antimicrobial genes (lys-7 and spp-1) and LYS-7::RFP. Meanwhile, intestinal ROS production could be enhanced by RNAi of acs-22, hmp-2, pkc-3, lys-7, and spp-1. Moreover, acs-22, hmp-2, and pkc-3 RNAi could inhibit innate immune response induced by 6-PPDQ. Additionally, lys-7 and spp-1 RNAi could strengthen intestinal permeability in 6-PPDQ exposed nematodes. Therefore, 6-PPDQ caused transgenerational intestinal toxicity, which was associated with both enhanced intestinal permeability and suppressed innate immunity.