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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 the liver of mice treated with BPA (1.2 mg/kg bw/day) for 5 days. (A) MDA concentrations (*P < 0.05 compared to control). (B) Catalase and GPx3 in the liver.
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Figure 4: Oxidative stress in the liver of mice treated with BPA (1.2 mg/kg bw/day) for 5 days. (A) MDA concentrations (*P < 0.05 compared to control). (B) Catalase and GPx3 in the liver.

Mentions: Mitochondrial function measured as the oxygen consumption rate significantly decreased 6 hr after BPA treatment (P = 0.03), but had recovered by 24 hr (Fig. 3E). Therefore, this showed that the changes in the levels of inflammatory cytokines and oxidative stress over time had a temporal association with hepatic mitochondrial dysfunction, and we hypothesized that BPA induced expression of proinflammatory cytokines, including in the liver, which might increase hepatic oxidative stress. Under BPA-treated conditions, hepatic antioxidant enzyme levels decreased; thus, hepatocytes could not be protected from BPA-induced oxidative stress resulting in mitochondrial dysfunction. To verify this hypothesis in the mice treated for 5 days, we measured MDA and found that MDA concentrations were elevated (Fig. 4A). Furthermore, the expression level of GPx3 decreased in the BPA-treated liver (Fig. 4B).


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 the liver of mice treated with BPA (1.2 mg/kg bw/day) for 5 days. (A) MDA concentrations (*P < 0.05 compared to control). (B) Catalase and GPx3 in the liver.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Oxidative stress in the liver of mice treated with BPA (1.2 mg/kg bw/day) for 5 days. (A) MDA concentrations (*P < 0.05 compared to control). (B) Catalase and GPx3 in the liver.
Mentions: Mitochondrial function measured as the oxygen consumption rate significantly decreased 6 hr after BPA treatment (P = 0.03), but had recovered by 24 hr (Fig. 3E). Therefore, this showed that the changes in the levels of inflammatory cytokines and oxidative stress over time had a temporal association with hepatic mitochondrial dysfunction, and we hypothesized that BPA induced expression of proinflammatory cytokines, including in the liver, which might increase hepatic oxidative stress. Under BPA-treated conditions, hepatic antioxidant enzyme levels decreased; thus, hepatocytes could not be protected from BPA-induced oxidative stress resulting in mitochondrial dysfunction. To verify this hypothesis in the mice treated for 5 days, we measured MDA and found that MDA concentrations were elevated (Fig. 4A). Furthermore, the expression level of GPx3 decreased in the BPA-treated liver (Fig. 4B).

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