PFOA and PFOS interact with superoxide dismutase and induce cytotoxicity in mouse primary hepatocytes: A combined cellular and molecular methods

Xu, Mengchen; Wan, Jingqiang; Niu, Qigui; Liu, Rutao

doi:10.1016/j.envres.2019.05.008

Cited by 78 publications

(22 citation statements)

References 45 publications

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“…We further used a functional animal model to confirm that deficiency of the AIM2 inflammasome protected mice from PFOS-induced tissue inflammation or asthmatic exacerbation. Surprisingly, we did not find the ROS production in macrophages; and this seems to be contradicted to some previous studies, showing PFOS-induced oxidative damage via mitochondria-dependent pathway 14 , 19 . The disagreement is attributed that the injury in hepatocytes may be a downstream effect of PFOS-induced macrophage activation, i.e., PFOS induces inflammatory cytokines or mediators released by macrophages and in turn to cause oxidative stress in the structural cells in liver tissue.…”

Section: Discussioncontrasting

confidence: 99%

“…Several studies have indicated that oxidative and inflammatory responses are involved in PFOS-induced cell injury and tissue damage. PFOS induces oxidative stress via inhibiting antioxidant factors (such as superoxide dismutase, lysozyme) or promoting reactive oxygen species in hepatocytes or endothelial cells, leading to cell death 11 , 13 , 14 , 16 , 17 . In addition, PFOS enhances the expression of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) in macrophages 18 , 19 .…”

Section: Introductionmentioning

confidence: 99%

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Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome

et al. 2021

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Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health, including inflammation in multiple organs, yet how PFAS are sensed by host cells, and how tissue inflammation eventually incurs, is still unclear. Here, we show that the double-stranded DNA receptor AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common form of PFAS, to trigger IL-1β secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome in a process involving mitochondrial DNA release through the Ca2+-PKC-NF-κB/JNK-BAX/BAK axis. Accordingly, Aim2−/− mice have reduced PFOS-induced inflammation, as well as tissue damage in the lungs, livers, and kidneys in both their basic condition and in an asthmatic exacerbation model. Our results thus suggest a function of AIM2 in PFOS-mediated tissue inflammation, and identify AIM2 as a major pattern recognition receptor in response to the environmental organic pollutants.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome

et al. 2021

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“…Each spectrum is the average of three consecutive scans. CD Pro software was employed for data analysis of secondary structure content (Xu et al 2019a).…”

Section: Research On the Changes Of Cat Conformationmentioning

confidence: 99%

Response of earthworm coelomocytes and catalase to pentanone and hexanone: a revelation of the toxicity of conventional solvents at the cellular and molecular level

Sun

et al. 2022

Environ Sci Pollut Res

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Organic solvents like 2-Pentanone and 2-Hexanone which are widely used in industrial production play an important role in the source of chemical pollution. Based on the current gaps in 2-Pentanone and 2-Hexanone cytotoxicity studies, the earthworms in the soil, which are susceptible to solvent leakage and volatilization, were selected as the receptor. The cytotoxicity of 2-Pentanone and 2-Hexanone was revealed by measuring the multiple intracellular indicators of oxidative stress. At the molecular level, changes in the structure and function of antioxidant enzyme catalase (CAT) were characterized in vitro by a variety of spectroscopy methods and molecular docking. The results show that 2-Pentanone and 2-Hexanone that induced the accumulation of intracellular reactive oxygen species can eventually decrease the cell viability of coelomocytes, accompanied by the regular changes of antioxidant activity and lipid peroxidation level. In addition, the exposure of 2-Pentanone and 2-Hexanone can shrink the backbone structure of CAT, quench the uorescence and misfold the secondary structure. The decrease in enzyme activity should be attributed to the structural changes induced by surface binding. This study discussed the toxicological effects and mechanisms of commonly used organic solvents at the cellular and molecular level, which creatively proposed a new combined method.

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“… 1 , 9 Previous data indicate that PFOA causes the death of primary and secondary hepatocytes. 17 – 19 Apoptosis is thought to be the main cell death pathway after exposure to PFOA. 18 – 20 Oxidative stress in hepatocytes after exposure to PFOA has been demonstrated by both in vitro and in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

“… 18 – 20 Oxidative stress in hepatocytes after exposure to PFOA has been demonstrated by both in vitro and in vivo studies. 5 , 19 In addition, a significant increase in inflammatory response markers interleukin 6 (IL-6), cyclooxygenase-2 (Cox-2) and C-reactive protein levels was detected in hepatic tissues. 5 However, the results are still conflicting, and the related mechanisms are controversial.…”

Section: Introductionmentioning

confidence: 99%

Determination of Perflourooctanoic Acid Toxicity in a Human Hepatocarcinoma Cell Line

Asadi

Öztaş

Özhan

2021

Journal of Health and Pollution

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Background. Perfluorooctanoic acid (PFOA) is used in different industrial and commercial products. Research shows the presence of PFOA in home dusts, tap and surface water, and in biological samples. The International Agency for Research on Cancer (IARC) has classified PFOA as a possible carcinogen for humans. The liver is thought to be a target organ of PFOA accumulation and toxicity. Objective. Some studies have found toxic effects on the liver and related mechanisms; however, more studies are needed to better understand PFOA - induced hepatotoxicity. Methods. In the present study, a human hepatocarcinoma cell line was exposed to PFOA for 24 hours and cell viability, apoptosis, the oxidative system and immune response were evaluated. Results. While apoptosis was the main cell death pathway at low concentration (86.5%), the necrotic cell fraction increased with higher concentrations (46.7%). Significant changes in the reactive oxygen species (5.3-folds) glutathione (GSH) (1.7-folds) and catalase (CAT) (1.4-folds) levels were observed, as well as changes to interleukin-6 (≤1.8-fold) and interleukin-8 levels (35–40%). Conclusions. In light of the data, PFOA is potentially hepatotoxic through the investigated pathways. The results represent a background for future in vivo mechanistic studies. Competing Interests. The authors declare no competing financial interests.

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PFOA and PFOS interact with superoxide dismutase and induce cytotoxicity in mouse primary hepatocytes: A combined cellular and molecular methods

Cited by 78 publications

References 45 publications

Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome

Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome

Response of earthworm coelomocytes and catalase to pentanone and hexanone: a revelation of the toxicity of conventional solvents at the cellular and molecular level

Determination of Perflourooctanoic Acid Toxicity in a Human Hepatocarcinoma Cell Line

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