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. 2021 Aug 17;11(31):210909.
doi: 10.5696/2156-9614-11.31.210909. eCollection 2021 Sep.

Determination of Perflourooctanoic Acid Toxicity in a Human Hepatocarcinoma Cell Line

Mahmoud Abudayyak  1   2 , Ezgi Öztaş  2 , Gül Özhan  2
Affiliations

Determination of Perflourooctanoic Acid Toxicity in a Human Hepatocarcinoma Cell Line

Mahmoud Abudayyak et al. J Health Pollut. .

Abstract

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.

Keywords: HepG2 cells; apoptosis; inflammation; oxidative stress; perfluorooctanoic acid.

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Figures

Figure 1
Figure 1
MTT results of perfluorooctanoic acid on HepG2 cells. Cell death (blue line) remained approximately 80% in higher concentrations. IC 50 value was calculated as 235.74 μM according to a logarithmic curve formula (orange line). Statistical evaluation was performed compared to the control group and results expressed as means.
Figure 2
Figure 2
Perfluorooctanoic acid-induced cell death measured by annex in V/PI staining and analyzed by flow cytometer. Apoptotic cells were decreased in higher concentrations, while necrotic cells were increased in a concentration-dependent manner. 100 μM H2O2 , as positive control, induced necrosis rather than apoptosis. The results were presented as a percentage of the total cell amount. Control cells were exposed to 1% DMSO. Statistical evaluation was performed compared to the control group and results are expressed as means.
Figure 3
Figure 3
Oxidative stress inducing potential of perfluorooctanoic acid on HepG2 cells. Perfluorooctanoic acid-induced ROS production was tested in all concentrations. 100 μM H2O2 was used as positive control. Control cells were exposed to 1% DMSO. Statistical evaluation was performed compared to the control group and results expressed as means.
Figure 4
Figure 4
Oxidative stress inducing potential of PFOA on HepG2 cells. Perfluorooctanoic acid increased GSH level only in the 10 μM concentration. 100 μM H2O2 was used as positive control. Control cells were exposed to 1% DMSO. Statistical evaluation was performed compared to the control group and results expressed as means.
Figure 5
Figure 5
Oxidative stress inducing potential of perfluorooctanoic acid on HepG2 cells. Perfluorooctanoic acid increased CAT activity only in 10 μM; 100 μM H2O2 was used as positive control. Control cells were exposed to 1% DMSO. Statistical evaluation was performed compared to the control group and results expressed as means.
Figure 6—
Figure 6—
Oxidative stress-inducing potential of perfluorooctanoic acid on HepG2 cells Superoxide dismutase activity remained unchanged after exposure to PFOA. 100 μM H2O2 was used as positive control. Control cells were exposed to 1% DMSO. Statistical evaluation was performed compared to the control group and results expressed as means.
Figure 7
Figure 7
IL-6 and IL-8 producing cells analyzed by flow cytometer. Perfluorooctanoic acid induced IL-6 in all concentrations tested; however, IL-8 levels were decreased in 25 and 50 μM. 25 μg/mL ConA was used as positive control and found to induce both IL-6 and IL-8 levels. Control cells were exposed to 1% DMSO. Statistical evaluation was performed compared to the control group and results expressed as means.
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