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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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Related in: MedlinePlus

Structure and function of hepatic mitochondria in the mice treated with 1.2 mg/kg bw/day of BPA for 5 days. (A) Morphology of hepatic mitochondria by transmission electron microscopy (150,000 × magnification). Control mice (A1) and BPA-treated mice (A2). Normal mitochondria (arrows) and swollen mitochondria (arrowheads). (B) Oxygen consumption rate of hepatic mitochondria. GMD, glutamate + malate + ADP; GMcD, GMD + cytochrome c; GMcDS, GMcD + succinate; FCCP, uncoupler (*P < 0.05 compared to control). (C) The respiratory complex I-V of hepatic mitochondria.
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Figure 1: Structure and function of hepatic mitochondria in the mice treated with 1.2 mg/kg bw/day of BPA for 5 days. (A) Morphology of hepatic mitochondria by transmission electron microscopy (150,000 × magnification). Control mice (A1) and BPA-treated mice (A2). Normal mitochondria (arrows) and swollen mitochondria (arrowheads). (B) Oxygen consumption rate of hepatic mitochondria. GMD, glutamate + malate + ADP; GMcD, GMD + cytochrome c; GMcDS, GMcD + succinate; FCCP, uncoupler (*P < 0.05 compared to control). (C) The respiratory complex I-V of hepatic mitochondria.

Mentions: There were no differences in the weight of the liver or its histology (studied by hematoxylin and eosin staining) between the control and BPA-treated mice (data not shown). However, the hepatic mitochondria in the mice treated with 1.2 mg/kg bw/day of BPA were much more swollen than those in the control mice, as viewed with transmission electron microscopy (Fig. 1A). The oxygen consumption rates (glutamate + malate + ADP [GMD], GMcD + succinate [GMcDS], and carbonylcyanide p-triflouromethoxyphenylhydrazone [FCCP]) were reduced in the hepatic mitochondria in the BPA-treated mice (Fig. 1B), especially state 3 respiration (GMD), which significantly decreased (P = 0.03). The expression of the respiratory complex III and V was also reduced in the BPA-treated mice compared to the control mice (Fig. 1C).


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)

Structure and function of hepatic mitochondria in the mice treated with 1.2 mg/kg bw/day of BPA for 5 days. (A) Morphology of hepatic mitochondria by transmission electron microscopy (150,000 × magnification). Control mice (A1) and BPA-treated mice (A2). Normal mitochondria (arrows) and swollen mitochondria (arrowheads). (B) Oxygen consumption rate of hepatic mitochondria. GMD, glutamate + malate + ADP; GMcD, GMD + cytochrome c; GMcDS, GMcD + succinate; FCCP, uncoupler (*P < 0.05 compared to control). (C) The respiratory complex I-V of hepatic mitochondria.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Structure and function of hepatic mitochondria in the mice treated with 1.2 mg/kg bw/day of BPA for 5 days. (A) Morphology of hepatic mitochondria by transmission electron microscopy (150,000 × magnification). Control mice (A1) and BPA-treated mice (A2). Normal mitochondria (arrows) and swollen mitochondria (arrowheads). (B) Oxygen consumption rate of hepatic mitochondria. GMD, glutamate + malate + ADP; GMcD, GMD + cytochrome c; GMcDS, GMcD + succinate; FCCP, uncoupler (*P < 0.05 compared to control). (C) The respiratory complex I-V of hepatic mitochondria.
Mentions: There were no differences in the weight of the liver or its histology (studied by hematoxylin and eosin staining) between the control and BPA-treated mice (data not shown). However, the hepatic mitochondria in the mice treated with 1.2 mg/kg bw/day of BPA were much more swollen than those in the control mice, as viewed with transmission electron microscopy (Fig. 1A). The oxygen consumption rates (glutamate + malate + ADP [GMD], GMcD + succinate [GMcDS], and carbonylcyanide p-triflouromethoxyphenylhydrazone [FCCP]) were reduced in the hepatic mitochondria in the BPA-treated mice (Fig. 1B), especially state 3 respiration (GMD), which significantly decreased (P = 0.03). The expression of the respiratory complex III and V was also reduced in the BPA-treated mice compared to the control mice (Fig. 1C).

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