Toxic Effects Of Perfluorooctanoic Acid Research Articles

Emerging perfluoroalkyl substances retard skeletal growth by accelerating osteoblasts senescence via ferroptosis

Due to the persistent nature and significant negative impacts of perfluorooctanoic acid (PFOA) on human health and other organisms, the emergence of new PFOA alternatives, such as perfluoro (2-methyl-3-oxhexanoic) acid (GenX) and perfluoro-3,6,9-trioxyundecanoic acid (PFO3TDA), have drawn significant attention. However, the toxic effects of PFOA and its substitutes on bones remain limited. In this study, we administered different concentrations of PFOA, GenX, and PFO3TDA via gavage to 3-week-old male BALB/C mice for four weeks. X-ray and micro-CT scans revealed shortening of the femur and tibia and significant reduction in bone density. Additionally, PFOA, GenX, and PFO3TDA promoted osteoblast senescence and impaired osteogenic capabilities. This was characterized by a decrease in the expression of osteogenesis-related genes (OCN, ALP, Runx2, etc.) and an increase in the expression of aging and inflammation-related factors (p16INK4a, P21, MMP3, etc). Furthermore, RNA sequencing revealed activation of the ferroptosis pathway in PFOA-treated osteoblasts, characterized by notable lipid peroxidation and excessive iron accumulation. Finally, by inhibiting the ferroptosis pathway with ferrostatin-1 (Fer-1), we effectively alleviated the senescence of MC3T3-E1 cells treated with PFOA, GenX, and PFO3TDA, and improved their osteogenic capabilities. Therefore, our study provides a new therapeutic insight into the impact of PFOA and its substitutes on bone growth and development.

Histological Assessment and Transcriptome Analysis Provide Insights into the Toxic Effects of Perfluorooctanoic Acid to Juvenile Half Smooth Tongue Sole Cynoglossus semilaevis

Histological Assessment and Transcriptome Analysis Provide Insights into the Toxic Effects of Perfluorooctanoic Acid to Juvenile Half Smooth Tongue Sole Cynoglossus semilaevis

Combined toxic effects of perfluorooctanoic acid and microcystin-LR on submerged macrophytes and biofilms

Perfluorooctanoic acid (PFOA) and microcystin-LR (MCLR) are pervasive pollutants in surface waters that induce significant toxic effects on aquatic organisms. However, the combined environmental risk of PFOA and MCLR remains unclear. To assess the toxic effects of PFOA and MCLR on submerged macrophytes and biofilms, Vallisneria natans was exposed to different concentrations of PFOA and MCLR (0.01, 0.1, 1.0 and 10.0 μg L−1). Vallisneria natans was sensitive to high concentrations of MCLR (10 μg L−1): plants exposed to 10 μg L−1 of MCLR measured a biomass of 3.46 g, which was significantly lower than the 8.71 g of the control group. Additionally, antagonistic interactive effects were observed in plants exposed to combined PFOA and MCLR. Exposure to these pollutants adversely affected photosynthesis of the plants and triggered peroxidation that promoted peroxidase, superoxide dismutase and catalase activities, and increased malondialdehyde and glutathione concentrations. The total chlorophyll content was lower in the highest concentration of the combined treatment group (0.443 mg g−1) than in the control group (0.534 mg g−1). Peroxidase activity increased from 662.63 U mg−1 Pr to 1193.45 U mg−1 Pr with increasing PFOA concentrations. Metabolomics indicated that the stress tolerance of Vallisneria natans was improved via altered fatty acid metabolism, hormone metabolism and carbon metabolism. Furthermore, PFOA and MCLR influenced the abundance and structure of the microbial community in the biofilms of Vallisneria natans. The increased contents of autoinducer peptide and N-acylated homoserine lactone signaling molecules indicated that these pollutants altered the formation and function of the biofilm. These results expand our understanding of the combined effects of PFOA and MCLR in aquatic ecosystems.

Perfluorooctanoic acid exposure and its neurodegenerative consequences in C57BL6/J mice.

Perfluorooctanoic acid (PFOA) is a member of Per- and polyfluoroalkyl substances (PFASs), an industrial pollutant that has been produced for decades and widely used in various industries. Accumulation of this compound in the environment and body of organisms led to increased concerns about this compound. The toxic effects of PFOA on the nervous system are unknown yet. We aimed to assess the myelination and neurogenesis in brain tissue. In this study, PFOA at doses of 1, 5, 10, and 20mg/kg were injected intraperitoneally into C57BL/6J mice for 14days, and the myelin content, CD4 + and CD8 + cell infiltration to brain regions were evaluated. Also, bromodeoxyuridine (BrdU) labeling was performed to compare neurogenesis among the groups. Luxol Fast Blue (LFB) staining revealed a significant decrease in myelin content in both sex at high concentrations (p < 0.001). The BrdU incorporation changes were observed in both sexes especially females which was highly related to the dose of PFOA and region of the brain. The infiltration rates of CD4 + and CD8 + cells to the brain were shown to be decreased; meanwhile the lymphocyte count was not significantly changed among groups over time and vice versa for the monocyte and neutrophils. Our results showed that PFOA had a negative impact on neurogenesis and the myelination process through the specific region of the brain depending on the dose and sex. Also, PFOA could disturb the number of CD4 + and CD8 + cells infiltrating the brain, which plays a crucial role in neurogenesis, leading to toxicity and neurological abnormalities. It seems that more research is needed to determine the exact mechanisms of PFOA neurotoxicity and its long-term behavioral consequences.

Non-targeted metabolomics of multiple human cells revealing differential toxic effects of perfluorooctanoic acid

Differences in toxic effects of contaminants among human cells are essential for evaluating their health risks to humans. In this study, non-targeted metabolomics of multiple human cell lines (A549 (lung), DLD-1 (intestine) and L-02 (liver) cells) was used to address the differential toxicity of perfluorooctanoic acid (PFOA). The number of differential metabolites (DMs) identified in the PFOA-treated A549 cells (67) was highest, followed by DLD-1 (12) and L-02 cells (10). The categorization of DMs was almost uniquely specific to each of cell lines. PFOA significantly promoted linoleic acid metabolism in L-02 cells whereas this metabolism was inhibited in the PFOA-treated A549 cells. The levels of interleukin (IL)-1β, IL-6, IL-8 and IL-13 were about 1.5 times higher in the PFOA-treated A549 and L-02 cells than in the controls. PFOA stimulated the biosynthesis of arginine and the metabolism of vitamin B6 in A549 cells. Arginine and vitamin B6 supplemented into cell culture effectively decreased the levels of IL-6 and IL-8. The inhibition of purine metabolism by PFOA resulted in the arrestation of DLD-1 cells at the G0/G1-phase. Our results suggest that the differential toxicity of PFOA related to exposure pathways could be elucidated by metabolic profiles specific to various human cells.

Mechanistic approach for the toxic effects of perfluorooctanoic acid on isolated rat liver and brain mitochondria

Perfluorooctanoic acid (PFOA) is one of the most widely used perfluoroalkanes as surfactants, lubricants and processing aids in the production of polymers, which has also been detected in the environment, wildlife and human body. Animal studies indicated that PFOA caused a wide array of toxic effects including liver and brain dysfunction, carcinogenicity and reproductive and developmental toxicity. Based on the established role of mitochondria-mediated pathways in the observed toxic effects of many drugs and chemicals, in this study, the potential toxic effects of PFOA on mitochondria isolated from rat liver and brain have been investigated. Mitochondria were isolated by differential centrifugation method and incubated with different concentrations of PFOA (0.5-1.5 mM). The effects of PFOA were assessed on a series of mitochondrial parameters including reactive oxygen species (ROS) formation, activities of mitochondrial complexes I/II/III, reduced glutathione (GSH) content, adenosine triphosphate (ATP) level, membrane potential, lipid peroxidation (LPO), mitochondrial swelling and cytochrome c release. The data on liver mitochondria indicated that PFOA-induced ROS elevation in both mitochondrial complexes I and III, mitochondrial membrane potential collapse, swelling, cytochrome c release and decreased ATP level which induces apoptosis or necrosis. On brain mitochondria, PFOA showed fairly similar effects on the above-mentioned parameters. However, different results were obtained when the effect of PFOA was assessed on LPO and complex II activity. Due to the fact that PFOA had toxic effects on the mitochondria isolated, it could be suggested that mitochondrial toxicity could be a plausible mechanism for the toxic effects of this fluorochemical on liver and brain function.

RETROSPECTIVE EXPOSURE ESTIMATION AND PREDICTED VERSUS OBSERVED SERUM PERFLUOROOCTANOIC ACID CONCENTRATIONS FOR PARTICIPANTS IN THE C8 HEALTH PROJECT

RETROSPECTIVE EXPOSURE ESTIMATION AND PREDICTED VERSUS OBSERVED SERUM PERFLUOROOCTANOIC ACID CONCENTRATIONS FOR PARTICIPANTS IN THE C8 HEALTH PROJECT

Disturbance of perfluorooctanoic acid on development and behavior in Drosophila larvae

Perfluorooctanoic acid (PFOA) is a well-known perfluorinated compound (PFC), and its toxicological impact is currently of worldwide concern. In this study, we sought to evaluate the potential biological effects and modes of action of PFOA in a range of physiologically and developmentally related phenotypes in the fruit fly Drosophila melanogaster. The results clearly indicated that the toxic effects of PFOA at the organismal level were associated with the developmental status of the organism, with larvae being most sensitive to this chemical. Except for the decreased weight of both sexes and the reduced longevity of male adults, PFOA had a robust effect on larval development, as determined by reduced body volume, aberrant foraging behavior, molting arrest, and polyphasic lethality. Remarkably, nutrient supplementation of the diet efficiently rescued the lethal effect of high PFOA concentrations on larval development. This result indicated that PFOA probably competed with nutritional components, leading to a disruption of the metabolic pathways responsible for larval development.

Elimination and toxicity of perfluorooctanoic acid during subchronic administration in the Wistar rat.

Perfluorinated fatty acids have been used commercially as corrosion inhibitors, wetting agents, fire extinguishers and surface active agents. In an earlier study the male rats were more susceptible to the toxic effects of perfluorooctanoic acid (PFO) than females. PFO-concentrations in the plasma suggested that there was a sex related difference in the urinary elimination rate. Active tubular secretion was observed only in the female kidney. The aim of the present study was to compare the urinary elimination of PFO between the two sexes during subchronic administration to the Wistar rat. PFO was administered by gavage to 48 newly-weaned animals at 0 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg for 28 consecutive days. The urine was collected on the 7th and 28th day of the study. At the end of the study, blood was collected by cardiac puncture. At necropsy, tissue specimens for histopathologic examination were collected from the controls and from the group receiving 30 mg/kg of PFO daily. Unlike the female rats, on the 7th day of the study all three groups of male rats excreted significant less PFO than their daily dose of PFO, which suggested that the males had not reached a steady state by seven days. On the 28th day, the males excreted an amount of PFO equal to their daily dose. The PFO concentrations in the plasma of the male animals suggested that the binding sites of PFO may become saturated at the chronic daily dose level of 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)