Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level.
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.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Min Kyong
MK
Moon
Min Joo
MJ
Kim
In Kyung
IK
Jung
Young Do
YD
Koo
Hwa Young
HY
Ann
Kwan Jae
KJ
Lee
Soon Hee
SH
Kim
Yeo Cho
YC
Yoon
Bong-Jun
BJ
Cho
Kyong Soo
KS
Park
Hak C
HC
Jang
Young Joo
YJ
Park
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds; D005979:Glutathione Peroxidase / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098826:Bisphenol A Compounds
D000255:Adenosine Triphosphate; D001559:Benzhydryl Compounds; D005979:Glutathione Peroxidase; D015850:Interleukin-6; D008315:Malondialdehyde; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; C116888:Gpx3 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds