Toxicological And Occupational Hazards Of Typical PFASs/OPEs Induced Renal Fibrosis And Adipocyte Differentiation

Since the reform and opening up,China’s rapid industrial development,brought about occupational health problems have become increasingly prominent,industrial development is inseparable from the wide application of chemical substances.Among them,all(poly)fluoroalkyl compounds(PFASs)and organophosphates(OPEs)used in industrial production will inevitably cause harm to humans,especially to front-line workers.Therefore,exploring its toxic effects and related mechanisms is conducive to solving the safety problems caused by occupational exposure and providing scientific basis for the prevention or treatment of caused diseases.The prevalence of chronic kidney disease and obesity is increasing worldwide,renal fibrosis is a common pathological feature of chronic kidney disease,and the enlargement and increase of fat cells leads to excessive fat accumulation in adipose tissue.Relevant studies have found that in addition to genetics,diet,habits and other factors,exposure to occupational hazards in work and production is also an important factor leading to chronic kidney disease and obesity.Perfluorooctane sulfonate(PFOS)and and Sodium p-perfluorous nonenoxybenzene sulfonate(OBS)were selected as typical perfluoroalkyl acid compounds,2-Ethylhexyl diphenyl phosphate(EHDPP)was selected as representatives of Organophosphate esters(OPEs),and rat normal renal fibroblast(NRK-49F)cells were selected as exposure objects to study the mechanism of induced fibrosis induced by PFOS and OBS in oxidative stress and gene expression.The toxic effect of EHDPP on promoting adipogenesis in preadipocyte(3T3-L1)fat formation was investigated from the aspects of cell morphology,adipogenic genes and regulatory factors.The main conclusions are as follows:(1)High concentrations of PFOS and OBS significantly affected cell proliferation.The level of intracellular ROS reactive oxygen species did not change significantly under PFOS exposure,while the level of intracellular reactive oxygen species in OBS-treated cells increased significantly at higher concentrations(50 μM,100 μM).The results of real-time PCR showed that the exposure of PFOS and OBS could significantly upregulate the marker genes α-SMA and FN associated with cell fibrosis,and there was a dose-dependent relationship.Transcriptome sequencing analysis was used to show that a certain concentration of PFOS and OBS exposure could significantly change the gene expression of NRK-49 F cells,and was significantly enriched in the pathway related to cellular fibrosis.Compared with PFOS,OBS has stronger cytotoxicity and fibrosis-inducing toxicity.(2)Lipid staining,triglyceride content,and adipogenic marker expression all showed that EHDPP promoted adipocyte differentiation.mi R-155-5p was the most pronounced miRNA downregulated by differential expression and decreased dose-dependently during EHDPP exposure.EHDPP exposure downregulated mi R-155-5p,thereby increasing C/EBPβ and peroxisome proliferator-activated receptor γ(PPARγ)expression and promoting adipogenesis in proadipocytes.The above results show that employees exposed to PFOS and OBS will face the risk of inducing changes in renal cell fibrotic factor levels,oxidative stress,etc.,and inducing chronic kidney disease.Exposure of fat cells to EHDPP will downregulate mi R-155-5p gene expression to induce obesity,which will provide scientific basis for the study of the toxic effects,pathogenesis and health risks of typical all-(poly)fluorinated organic compounds and organophosphates.