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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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Changes in the levels of oxidative stress and inflammatory cytokines at 1, 6, and 24 hr after a single injection of BPA (1.2 mg/kg bw/day). (A) MDA concentrations in the liver. (B) Catalase and GPx3 in the liver. (C) IL-6 and TNF-α levels in the liver. (D) Serum IL-6 and TNF-α levels. (E) Oxygen consumption rate in hepatic mitochondria. GMD, glutamate + malate + ADP; GMcD, GMD + cytochrome c; GMcDS, GMcD + succinate (*P < 0.05 compared to control).
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Figure 3: Changes in the levels of oxidative stress and inflammatory cytokines at 1, 6, and 24 hr after a single injection of BPA (1.2 mg/kg bw/day). (A) MDA concentrations in the liver. (B) Catalase and GPx3 in the liver. (C) IL-6 and TNF-α levels in the liver. (D) Serum IL-6 and TNF-α levels. (E) Oxygen consumption rate in hepatic mitochondria. GMD, glutamate + malate + ADP; GMcD, GMD + cytochrome c; GMcDS, GMcD + succinate (*P < 0.05 compared to control).

Mentions: The hepatic concentration of MDA, which is a product of lipid peroxidation, was measured as an indicator of oxidative stress. After a single injection of BPA, MDA concentrations gradually increased over time for 6 hr (P = 0.04) (Fig. 3A), while the hepatic expression of GPx3, an important antioxidant enzyme, decreased over the same period (Fig. 3B). In contrast, the expression of catalase remained unchanged. Because inflammatory cytokines can induce oxidative stress, we measured the hepatic expression of IL-6 and TNF-α. IL-6 expression increased 1 and 6 hr after BPA injection, suggesting a pathogenic role, while the expression of TNF-α was unchanged (Fig. 3C). Serum IL-6 and TNF-α levels showed similar results (P < 0.01, P = 0.02 respectively) (Fig. 3D).


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)

Changes in the levels of oxidative stress and inflammatory cytokines at 1, 6, and 24 hr after a single injection of BPA (1.2 mg/kg bw/day). (A) MDA concentrations in the liver. (B) Catalase and GPx3 in the liver. (C) IL-6 and TNF-α levels in the liver. (D) Serum IL-6 and TNF-α levels. (E) Oxygen consumption rate in hepatic mitochondria. GMD, glutamate + malate + ADP; GMcD, GMD + cytochrome c; GMcDS, GMcD + succinate (*P < 0.05 compared to control).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Changes in the levels of oxidative stress and inflammatory cytokines at 1, 6, and 24 hr after a single injection of BPA (1.2 mg/kg bw/day). (A) MDA concentrations in the liver. (B) Catalase and GPx3 in the liver. (C) IL-6 and TNF-α levels in the liver. (D) Serum IL-6 and TNF-α levels. (E) Oxygen consumption rate in hepatic mitochondria. GMD, glutamate + malate + ADP; GMcD, GMD + cytochrome c; GMcDS, GMcD + succinate (*P < 0.05 compared to control).
Mentions: The hepatic concentration of MDA, which is a product of lipid peroxidation, was measured as an indicator of oxidative stress. After a single injection of BPA, MDA concentrations gradually increased over time for 6 hr (P = 0.04) (Fig. 3A), while the hepatic expression of GPx3, an important antioxidant enzyme, decreased over the same period (Fig. 3B). In contrast, the expression of catalase remained unchanged. Because inflammatory cytokines can induce oxidative stress, we measured the hepatic expression of IL-6 and TNF-α. IL-6 expression increased 1 and 6 hr after BPA injection, suggesting a pathogenic role, while the expression of TNF-α was unchanged (Fig. 3C). Serum IL-6 and TNF-α levels showed similar results (P < 0.01, P = 0.02 respectively) (Fig. 3D).

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