Perfluorooctanoic acid exposure triggers oxidative stress in the mouse pancreas

Kamendulis, Lisa M.; Wu, Qiangen; Sandusky, George E.; Hocevar, Barbara A.

doi:10.1016/j.toxrep.2014.07.015

Cited by 52 publications

(38 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, it was found that ¼ LC 50 and LC 50 PFOA (28.2 and 112.8 μM, respectively) caused apoptosis and necrosis in fetal mouse oocytes in vitro after their exposure for 24 hours to the PFC. The observed oocyte cytotoxicity of PFOA is probably related to induction of apoptosis via intracellular ROS generation, as it has been reported in other cell types . Excess ROS would lead to lipid peroxidation, protein degradation and DNA damage, which eventually would result in oocyte death …”

Section: Discussionmentioning

confidence: 59%

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

López-Arellano

Luna

et al. 2018

Environmental Toxicology

View full text Add to dashboard Cite

Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acid family of compounds. Due to the presence of strong carbon-fluorine bonds, it is practically nonbiodegradable and highly persistent in the environment. PFOA has been detected in the follicular fluid of women, and positively associated with reduced fecundability and infertility. However, there are no reports concerning the experimental evaluation of PFOA on oocyte toxicity in mammals. The aim of the present study was to determine if PFOA is able to induce oxidative stress in fetal ovaries and cause apoptosis in oocytes in vitro. In addition, since inhibition of the gap junction intercellular communication (GJIC) by PFOA has been demonstrated in liver cells in vivo and in vitro, the effect of PFOA on the GJIC between the oocyte and its supportive cumulus cells was studied.Results show that PFOA induced oocyte apoptosis and necrosis in vitro (medium lethal concentration, LC 50 = 112.8 μM), as evaluated with Annexin-V-Alexa 508 in combination with BOBO-1 staining. Reactive oxygen species (ROS) levels, as assessed by DCFH-DA, increased significantly in fetal ovaries exposed to ¼ LC 50 (28.2 μM, a noncytotoxic and relevant occupational exposure concentration) and LC 50 PFOA ex vivo. This perfluorinated compound also caused the blockage of GJIC in cumulus cells-oocyte complexes (COCs) obtained from female mice exposed in vivo, as evaluated by calcein transfer from cumulus cells to the oocyte. The ability of PFOA of disrupting the GJIC in COCs, generating ROS in the fetal ovary and causing apoptosis and necrosis in mammal's oocytes, might account for the reported association between increasing maternal plasma concentrations of PFOA with reduced fertility in women.

show abstract

Section: Discussionmentioning

confidence: 59%

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

López-Arellano

Luna

et al. 2018

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…ROS are reactive molecules or free radicals that generated as a byproduct of normal aerobic metabolism, and the production of ROS has been regarded as a possible toxicity mechanism of polluted water in aquatic organisms [29]. Under normal physiological conditions, these highly reactive substances can be continually balanced by the antioxidant defense system comprising of antioxidant enzymes like superoxide dismutase (SOD) and low-molecular-weight scavengers like reduced glutathione (GSH).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of single and joint toxicity of perfluorooctane sulfonate and zinc to Limnodrilus hoffmeisteri : Acute toxicity, bioaccumulation and oxidative stress

Liu

Yan

et al. 2016

Journal of Hazardous Materials

View full text Add to dashboard Cite

“…In mouse testis, the lowest dose tested of 2.5 mg/kg/day PFOA increased MDA and hydrogen peroxide levels, decreased the expression of the oxidant-sensitive transcription factor, Nrf2, and inhibited the activities of antioxidant enzymes (superoxide dismutase and catalase) [91]. PFOA also induces oxidative stress in a dose-dependent manner from 0.5 to 5 mg/kg/day in the mouse liver and pancreas [25], and a variety of tissues including rat pancreatic β-cells [92], mouse testes and epididymis [93], and mouse ovary [94]. Similarly, in vivo and in vitro studies have demonstrated that PFOS exposure results in oxidative stress, evidenced by the production of ROS, changes in antioxidant enzymes, elevation of lipid peroxidation products and changes in Nrf2 [32,[95][96][97].…”

Section: Induces Oxidative Stressmentioning

confidence: 91%

“…Unlike organochlorine aromatic compounds such as polychlorinated biphenyls, chlorinated dioxins and dichlorodiphenyltrichloroethane (DDT), PFAS are not lipophilic and do not accumulate in adipose tissue [24]. In vivo, PFAS bind to proteins in the blood such as albumin and have been detected in tissues including the liver, pancreas, kidney, lung and brain [25,26]. PFAS readily cross the placenta and are detected in cord blood and fetal tissues, as well as in breast milk [27,28].…”

Section: Existing Research On Pfas Exposure and Cancer Riskmentioning

confidence: 99%

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Temkin

Hocevar

Andrews

et al. 2020

IJERPH

Self Cite

View full text Add to dashboard Cite

Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.

show abstract

Perfluorooctanoic acid exposure triggers oxidative stress in the mouse pancreas

Abstract: HighlightsPFOA triggers focal ductal hyperplasia following 7 day exposure.PFOA exposure increases 8-iso-PGF2α levels in the pancreas.Antioxidant gene expression is upregulated in the pancreas following PFOA exposure.

Cited by 52 publications

References 45 publications

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

Evaluation of single and joint toxicity of perfluorooctane sulfonate and zinc to Limnodrilus hoffmeisteri : Acute toxicity, bioaccumulation and oxidative stress

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Contact Info

Product

Resources

About