Early-Life Exposure to Bisphenol A Induces Liver Injury in Rats Involvement of Mitochondria-Mediated Apoptosis

Xia, Wei; Jiang, Ying; Li, Yuanyuan; Wan, Yanjian; Liu, Juan; Ma, Yue; Mao, Zhenxing; Chang, Huailong; Li, Gengqi; Xu, Bing; Chen, Xi; Xu, Shunqing

doi:10.1371/journal.pone.0090443

Cited by 74 publications

(59 citation statements)

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“…Exposure to BPA in adult rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis (8). BPA exposure causes abnormalities of liver function and hepatic damage associated with mitochondrial apoptosis (9). Further, low doses of BPA and exposure during maternal stage induced lipid accumulation and production of reactive oxygen species in the hepatic and testis mitochondria, respectively (10,11).…”

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confidence: 99%

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Agarwal

Yadav

Tiwari

et al. 2016

Journal of Biological Chemistry

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The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs). It also inhibited hippocampal derived NSC proliferation and differentiation, as evident by the decreased number of BrdU-and ␤-III tubulin-positive cells. All these effects were reversed by the inhibition of oxidative stress using N-acetyl cysteine. BPA up-regulated the levels of Drp-1 (dynamin-related protein 1) and enhanced its mitochondrial translocation, with no effect on Fis-1, Mfn-1, Mfn-2, and Opa-1 in vitro and in the hippocampus. Moreover, transmission electron microscopy studies suggested increased mitochondrial fission and accumulation of fragmented mitochondria and decreased elongated mitochondria in the hippocampus of the rat brain. Impaired mitochondrial dynamics by BPA resulted in increased reactive oxygen species and malondialdehyde levels, disruption of mitochondrial membrane potential, and ATP decline. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions, fragmentation, and apoptosis. Interestingly, BPAmediated inhibitory effects on NSC proliferation and neuronal differentiations were also mitigated by Drp-1 inhibition. On the other hand, Drp-1 inhibition blocked BPA-mediated Drp-1 translocation, leading to decreased apoptosis of NSC. Overall, our studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus.

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confidence: 99%

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Agarwal

Yadav

Tiwari

et al. 2016

Journal of Biological Chemistry

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“…Moreover, similar findings were observed in the liver of rats treated with BPA (Xia et al . ). Nevertheless, other researchers revealed that the mode of cell death due to BPA changed from apoptosis to necrosis and this was also associated with caspase activation (Li et al .…”

Section: Discussionmentioning

confidence: 97%

Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat

Ibrahim

Elbakry

Bayomy

2016

Int J Experimental Path

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SUMMARYBisphenol A (BPA) is a synthetic oestrogen that is extensively used in a wide range of daily used plastic products. This makes it one of the environmental chemicals that may have impact on human health. Due to its oestrogenic effect, BPA might affect the mammary gland. This study aimed to investigate the influence of BPA on the histological structure of the mammary gland of the adult female albino rat and its effect on epithelial cell proliferation and apoptosis status, in addition to its possible modulating effect on estrogen receptor expression. Thirty female adult albino rats were divided into control and experimental groups. The rats in the experimental group were gavaged with 5 mg/kg BPA daily for 8 weeks. The mammary glands were dissected and processed for histological and immunohistochemical stains for Ki-67, activated caspase-3 and estrogen receptor alpha (ER-a). BPA induced an increase in the number and size of the acini and ducts in the mammary gland of treated rats with hyperplasia of their lining epithelial cells. The collagen fibre content was significantly increased in the connective tissue stroma separating the ducts. Immunohistochemical results showed a significant increase in Ki-67 and caspase-3, but a nonsignificant increase in ER-a expression. Bisphenol A induced structural changes and affected the proliferation rate of mammary glands, so it might be one of the predisposing factors for breast cancer.

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“…15 BPA induces mitochondrial dysfunction and this has been linked to BPA-associated inflammation. [34][35][36][37] Urinary BPA concentration, a marker of BPA exposure in the general population, is associated with markers of oxidative stress (malondialdehyde and 8-hydroxydeoxyguanosine) and inflammation (white blood cell count and CRP levels) in certain subpopulations such as postmenopausal and pregnant women. 30,38,39 In this regard, we found evidence of higher oxidative stress and inflammation in patients on hemodialysis dialyzed with BPAcontaining polysulfone membranes than with BPA-free polynephron membranes.…”

Section: Discussionmentioning

confidence: 99%

The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood

Bosch-Panadero¹,

Mas

Sanchez-Ospina

et al. 2015

JASN

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Bisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.866.8 to 69.1610.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.668.4 to 47.167.5 ng/ml, P,0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.03960.002 to 0.04360.001 ng/10 6 cells, P,0.01), but decreased with polynephron dialyzers (from 0.04560.001 to 0.03660.001 ng/10 6 cells, P,0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro, polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.

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Early-Life Exposure to Bisphenol A Induces Liver Injury in Rats Involvement of Mitochondria-Mediated Apoptosis

Cited by 74 publications

References 50 publications

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat

The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood

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