Chronic exposure to environmentally relevant levels of di(2-ethylhexyl) phthalate (DEHP) disrupts lipid metabolism associated with SBP-1/SREBP and ER stress in C. elegans.

DEHP is commonly found in the environment, biota, food, and humans, raising significant health concerns. Whether developmental stage and exposure duration modify the obesogenic effects of DEHP is unclear, especially the underlying mechanisms by which chronic exposure to DEHP as well as its metabolites remain largely unknown. This study investigated the obesogenic effects of chronic DEHP exposure, with levels below environmentally-relevant amounts and provide the mechanism in Caenorhabditis elegans. We show that early-life DEHP exposure resulted in an increased lipid and triglyceride (TG) accumulation mainly attributed to DEHP itself, not its metabolite mono-2-ethylhexyl phthalate (MEHP). In addition, developmental stage and exposure timing influence DEHP-induced TG accumulation and chronic DEHP exposure resulted in the most significant effect. Analysis of fatty acid composition shows that chronic DEHP exposure altered fatty acid composition and TG, resulting in an increased ω-6/ω-3 ratio. The increased TG content by chronic DEHP exposure required lipogenic genes fat-6, fat-7, pod-2, fasn-1, and sbp-1. Moreover, chronic DEHP exposure induced XBP-1-mediated endoplasmic reticulum (ER) stress which might lead to up-regulation of sbp-1. This study suggests the possible involvement of ER stress and SBP-1/SREBP-mediated lipogenesis in chronic DEHP-induced obesogenic effects. Results from this study implies that chronic exposure to DEHP disrupts lipid metabolism, which is likely conserved across species due to evolutionary conservation of molecular mechanisms, raising concerns in ecological and human health.

Early-life and chronic exposure to di(2-ethylhexyl) phthalate enhances amyloid-ß toxicity associated with an autophagy-related gene in Caenorhabditis elegans Alzheimer's disease models.

The widespread use of di(2-ethylhexyl) phthalate (DEHP) has resulted in its ubiquitous presence in the environment, which has led to serious health concerns. One of these concerns is its possible link to Alzheimer's disease (AD), which is the most common neurodegenerative disease in aged individuals. This study investigated whether early-life and chronic exposure to DEHP affects AD via the toxicity of amyloid-ß (Aß), which has been implicated in the pathogenesis of AD, using Caenorhabditis elegans AD models (strains CL4176 and CL2006). We show that early-life DEHP exposure increased Aß toxicity in C. elegans strains CL4176 and CL2006. Early-life and chronic exposure to DEHP also significantly increased intracellular ROS levels and Aß deposition in aged CL2006 nematodes. Moreover, it was found that DEHP-induced Aß toxicity does not require transcription factors DAF-16 or SKN-1, while early-life and chronic exposure to DEHP significantly increased the accumulation of lysosome-related organelles and the mRNA levels of the autophagy-related gene bec-1 in aged CL2006 nematodes. Our findings suggest that early-life and chronic exposure to DEHP enhances Aß toxicity, which may be associated with the autophagy-lysosomal degradation pathway in C. elegans.

Chronic ZnO-NPs exposure at environmentally relevant concentrations results in metabolic and locomotive toxicities in Caenorhabditis elegans.

ZnO nanoparticles (ZnO-NPs) are emerging contaminants that raise the concerns of potential risk in the aquatic environment. It has been estimated that the environmental ZnO-NPs concentration is 76 µg/l in the aquatic environment. Our aim was to determine the aquatic toxicity of ZnO-NPs with chronic exposure at environmentally relevant concentrations using the nematode Caenorhabditis elegans. Two simulated environmentally relevant mediums-moderately hard reconstituted water (EPA water) and simulated soil pore water (SSPW)-were used to represent surface water and pore water in sediment, respectively. The results showed that the ZnO-NPs in EPA water has a much smaller hydrodynamic diameter than that in SSPW. Although the ionic release of Zn ions increased time-dependently in both mediums, the Zn ions concentrations in EPA water increased two-fold more than that in SSPW at 48 h and 72 h. The ZnO-NPs did not induce growth defects or decrease head thrashes in C. elegans in either media. However, chronic exposure to ZnO-NPs caused a significant reduction in C. elegans body bends in EPA water even with a relatively low concentration (0.05 µg/l); similar results were not observed in SSPW. Moreover, at the same concentrations (50 and 500 µg/l), body bends in C. elegans were reduced more severely in ZnO-NPs than in ZnCl2 in EPA water. The ATP levels were consistently and significantly decreased, and ROS was induced after ZnO-NPs exposure (50 and 500 µg/l) in EPA water. Our results provide evidences that chronic exposure to ZnO-NPs under environmentally relevant concentrations causes metabolic and locomotive toxicities implicating the potential ecotoxicity of ZnO-NPs at low concentrations in aquatic environments.

Selenite protects Caenorhabditis elegans from oxidative stress via DAF-16 and TRXR-1.

SCOPE: Selenium is an essential micronutrient. In the present study, trace amount of selenite (0.01 µM) was evaluated for oxidative stress resistance and potential associated factors in Caenorhabditis elegans. METHODS AND RESULTS: Selenite-treated C. elegans showed an increased survival under oxidative stress and thermal stress compared to untreated controls. Further studies demonstrated that the significant stress resistance of selenite on C. elegans could be attributed to its in vivo free radical-scavenging ability. We also found that the oxidative and thermal stress resistance phenotypes by selenite were absent from the forkhead transcription factor daf-16 mutant worms. Moreover, selenite influenced the subcellular distribution of DAF-16 in C. elegans. Furthermore, selenite increased mRNA levels of stress-resistance-related proteins, including superoxide dismutase-3 and heat shock protein-16.2. Additionally, selenite (0.01 µM) upregulated expressions of transgenic C. elegans carrying sod-3::green fluorescent protein (GFP) and hsp-16.2::GFP, whereas this effect was abolished by feeding daf-16 RNA interference in C. elegans. Finally, unlike the wild-type N2 worms, the oxidative stress resistance phenotypes by selenite were both absent from the C. elegans selenoprotein trxr-1 mutant worms and trxr-1 mutants feeding with daf-16 RNA interference. CONCLUSION: These findings suggest that the antioxidant effects of selenite in C. elegans are mediated via DAF-16 and TRXR-1.