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Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level.

Moon MK, Kim MJ, Jung IK, Koo YD, Ann HY, Lee KJ, Kim SH, Yoon YC, Cho BJ, Park KS, Jang HC, Park YJ - J. Korean Med. Sci. (2012)

Bottom Line: Bisphenol A (BPA) has been reported to possess hepatic toxicity.The expression levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) also increased.In HepG2 cells, 10 or 100 nM of BPA also decreased the oxygen consumption rate, ATP production, and the mitochondrial membrane potential.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
Bisphenol A (BPA) has been reported to possess hepatic toxicity. We investigated the hypothesis that BPA, below the no observed adverse effect level (NOAEL), can induce hepatic damage and mitochondrial dysfunction by increasing oxidative stress in the liver. Two doses of BPA, 0.05 and 1.2 mg/kg body weight/day, were administered intraperitoneally for 5 days to mice. Both treatments impaired the structure of the hepatic mitochondria, although oxygen consumption rate and expression of the respiratory complex decreased only at the higher dose. The hepatic levels of malondialdehyde (MDA), a naturally occurring product of lipid peroxidation, increased, while the expression of glutathione peroxidase 3 (GPx3) decreased, after BPA treatment. The expression levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) also increased. In HepG2 cells, 10 or 100 nM of BPA also decreased the oxygen consumption rate, ATP production, and the mitochondrial membrane potential. In conclusion, doses of BPA below the NOAEL induce mitochondrial dysfunction in the liver, and this is associated with an increase in oxidative stress and inflammation.

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Oxidative stress in HepG2 cells treated with 100 nM BPA. (A) MDA concentrations determined by a TBARS assay kit. (B) Fluorescence after the ROS-sensitive indicator DHE staining. Control (B1), 2 hr (B2), 6 hr (B3), and 24 hr (B4) after the treatment of 100 nM BPA.
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Figure 7: Oxidative stress in HepG2 cells treated with 100 nM BPA. (A) MDA concentrations determined by a TBARS assay kit. (B) Fluorescence after the ROS-sensitive indicator DHE staining. Control (B1), 2 hr (B2), 6 hr (B3), and 24 hr (B4) after the treatment of 100 nM BPA.

Mentions: To confirm the effects of BPA on hepatic mitochondria in vitro, HepG2 cells were treated with 2 different concentrations of BPA (10 nM and 100 nM). Treatment of HepG2 cells with BPA for 2 hr lead to a deteriorated mitochondrial architecture (Fig. 6A), and this was more severe in the 100 nM-treated mice than the 10 nM-treated HepG2 cell. Not only the morphology but also the function of the mitochondria was impaired by BPA treatment; oxygen consumption rates were reduced according to the dose (Fig. 6B). These results were replicable between 3 separate experiments. We also measured other parameters of mitochondrial function and observed the same results; ATP consumption (Fig. 6C) and MMP (Fig. 6D) were reduced after BPA treatment. To exclude the possibility that cell death caused the mitochondrial dysfunction, a cell viability assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was performed, and no cell death was observed (data not shown). To confirm the increase of oxidative stress by BPA in hepatocytes, we measured the MDA concentrations (Fig. 7A) and DHE activities (Fig. 7B), and BPA increased both of them.


Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level.

Moon MK, Kim MJ, Jung IK, Koo YD, Ann HY, Lee KJ, Kim SH, Yoon YC, Cho BJ, Park KS, Jang HC, Park YJ - J. Korean Med. Sci. (2012)

Oxidative stress in HepG2 cells treated with 100 nM BPA. (A) MDA concentrations determined by a TBARS assay kit. (B) Fluorescence after the ROS-sensitive indicator DHE staining. Control (B1), 2 hr (B2), 6 hr (B3), and 24 hr (B4) after the treatment of 100 nM BPA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369451&req=5

Figure 7: Oxidative stress in HepG2 cells treated with 100 nM BPA. (A) MDA concentrations determined by a TBARS assay kit. (B) Fluorescence after the ROS-sensitive indicator DHE staining. Control (B1), 2 hr (B2), 6 hr (B3), and 24 hr (B4) after the treatment of 100 nM BPA.
Mentions: To confirm the effects of BPA on hepatic mitochondria in vitro, HepG2 cells were treated with 2 different concentrations of BPA (10 nM and 100 nM). Treatment of HepG2 cells with BPA for 2 hr lead to a deteriorated mitochondrial architecture (Fig. 6A), and this was more severe in the 100 nM-treated mice than the 10 nM-treated HepG2 cell. Not only the morphology but also the function of the mitochondria was impaired by BPA treatment; oxygen consumption rates were reduced according to the dose (Fig. 6B). These results were replicable between 3 separate experiments. We also measured other parameters of mitochondrial function and observed the same results; ATP consumption (Fig. 6C) and MMP (Fig. 6D) were reduced after BPA treatment. To exclude the possibility that cell death caused the mitochondrial dysfunction, a cell viability assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was performed, and no cell death was observed (data not shown). To confirm the increase of oxidative stress by BPA in hepatocytes, we measured the MDA concentrations (Fig. 7A) and DHE activities (Fig. 7B), and BPA increased both of them.

Bottom Line: Bisphenol A (BPA) has been reported to possess hepatic toxicity.The expression levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) also increased.In HepG2 cells, 10 or 100 nM of BPA also decreased the oxygen consumption rate, ATP production, and the mitochondrial membrane potential.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
Bisphenol A (BPA) has been reported to possess hepatic toxicity. We investigated the hypothesis that BPA, below the no observed adverse effect level (NOAEL), can induce hepatic damage and mitochondrial dysfunction by increasing oxidative stress in the liver. Two doses of BPA, 0.05 and 1.2 mg/kg body weight/day, were administered intraperitoneally for 5 days to mice. Both treatments impaired the structure of the hepatic mitochondria, although oxygen consumption rate and expression of the respiratory complex decreased only at the higher dose. The hepatic levels of malondialdehyde (MDA), a naturally occurring product of lipid peroxidation, increased, while the expression of glutathione peroxidase 3 (GPx3) decreased, after BPA treatment. The expression levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) also increased. In HepG2 cells, 10 or 100 nM of BPA also decreased the oxygen consumption rate, ATP production, and the mitochondrial membrane potential. In conclusion, doses of BPA below the NOAEL induce mitochondrial dysfunction in the liver, and this is associated with an increase in oxidative stress and inflammation.

Show MeSH
Related in: MedlinePlus