Involvement of Oxidative Stress and Inflammation in Liver Injury Caused by Perfluorooctanoic Acid Exposure in Mice

Yang, Bei; Wu, Zhongze; Hu, Zhenzhen; Liu, Fangming; Yang, Shu‐Long; Kuang, Haibin; Wu, Lei; Wei, Jie; Wang, Jinglei; Zou, Ting; Zhang, Dalei

doi:10.1155/2014/409837

Cited by 32 publications

(33 citation statements)

References 41 publications

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“…In this study, protein levels of HSPs (except spot 281) were all induced in the high PFDoA dose group, indicating that a certain degree of oxidative stress might occur in rat liver exposed to PFDoA. Multiple studies have demonstrated that PFAS exposure can induce excessive ROS in various cells (Eriksen et al 2010;Liu et al 2007;Reistad et al 2013;Yang et al 2014). In our study, ROS content increased in rat primary hepatocytes exposed to PFDoA.…”

Section: Discussionsupporting

confidence: 57%

Activation of peroxisome proliferator-activated receptor α ameliorates perfluorododecanoic acid-induced production of reactive oxygen species in rat liver

et al. 2015

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Perfluorododecanoic acid (PFDoA) is a ubiquitous environmental pollutant known to cause hepatocellular hypertrophy; however, the mechanisms of hepatotoxicity remain poorly understood. In this study, male rats were exposed to 0, 0.05, 0.2 and 0.5 mg/kg/day of PFDoA for 110 days. After two-dimensional differential gel electrophoresis and MALDI-TOF/TOF analysis, 73 differentially expressed proteins involved in lipid metabolism, inflammation, stress response and other functions were successfully identified. Among them, six significantly changed proteins (CTE1, MTE1, HADHA, ECH1, ALDH2 and CPS1) were found to be regulated by peroxisome proliferator-activated receptor alpha (PPARα). The anti-oxidant enzyme activity assays of superoxide dismutase and glutathione peroxidase and the content of thiobarbituric acid-reactive substances in the liver implied that PFDoA caused oxidative stress. The mRNA levels of PPARα in rat primary hepatocytes were knocked down by lentivirus-mediated RNAi. Furthermore, targeted protein levels of CTE1 and MTE1 were down-regulated, while those of HADHA, ALDH2 and CPS1 were up-regulated. After PFDoA exposure, however, the targeted protein levels of CTE1 and ALDH2 increased compared with those of the knockdown untreated group. The reactive oxygen species (ROS) content in rat hepatocytes assayed by flow cytometry significantly increased in the PPARα knockdown groups, consistent with the PPARα antagonist GW6471- and agonist WY14643-treated groups. These results strongly suggested that PPARα played an important role in suppressing ROS content in hepatocytes following PFDoA exposure.

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Section: Discussionsupporting

confidence: 57%

Activation of peroxisome proliferator-activated receptor α ameliorates perfluorododecanoic acid-induced production of reactive oxygen species in rat liver

et al. 2015

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“…It has been revealed that exposure to PFOA can generate reactive oxygen species (ROS) and induce oxidative stress in normal mammalian cells [40][41][42]. We also reported previously that exposure to PFOA caused oxidative stress in the liver of mice [20].…”

Section: Discussionmentioning

confidence: 80%

“…After 1 week of acclimatization, mice were orally administrated with different concentrations of PFOA (2.5, 5 or 10 mg/kg/day) once daily for 14 consecutive days. The doses of PFOA (2.5-10 mg/kg/day) were chosen based on the previous observations [18][19][20]. Controls received an equivalent volume of water.…”

Section: Treatmentsmentioning

confidence: 99%

Involvement of NRF2 in Perfluorooctanoic Acid-Induced Testicular Damage in Male Mice1

Liu¹,

Yang²,

Wu³

et al. 2015

Biology of Reproduction

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Perfluorooctane acid (PFOA) is a hazardous environmental pollutant that has been reported to exert adverse effects on animal and human health. In this study, male mice were orally administered different concentrations of PFOA (2.5, 5, or 10 mg/kg/day) to evaluate the reproductive toxicity. Exposure to PFOA for 14 consecutive days obviously disrupted seminiferous tubules and reduced sperm count. The highest concentration of PFOA (10 mg/kg/day) caused growth retardation and diminished absolute testis weight. Furthermore, PFOA treatment significantly increased the generation of oxidative stress indicators malondialdehyde and hydrogen peroxide, decreased the expression of transcription factor NRF2, and inhibited the activities of antioxidant enzymes superoxide dismutase and catalase in the testis. Moreover, PFOA exposure up-regulated p-p53 and BAX expression and down-regulated BCL-2 expression in the testis. These results indicated that PFOA-induced male reproductive disorders might be involved in developmental impairment and inhibition of NRF2-mediated antioxidant response in the testis of mice.

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“…In particular, exposure to PFOA appears to deplete glutathione reserves and epigentically alters glutathione transferase expression [72], increasing the risk of oxidative damage focused on tissues like the liver [73]. Among the elevated inflammatory mediators contributing to hepatic damage are IL-6, cyclooxygenase-2, and C-reactive protein [74]. Adding to the risk, the hepatic inflammatory damage induced by PFOA is exacerbated by a high-fat diet intake [73].…”

Section: Perfluorinated Chemicalsmentioning

confidence: 99%

Effects of Endocrine Disrupters on Immune Function and Inflammation

Dietert¹

2015

Endocrine Disruption and Human Health

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Involvement of Oxidative Stress and Inflammation in Liver Injury Caused by Perfluorooctanoic Acid Exposure in Mice

Cited by 32 publications

References 41 publications

Activation of peroxisome proliferator-activated receptor α ameliorates perfluorododecanoic acid-induced production of reactive oxygen species in rat liver

Activation of peroxisome proliferator-activated receptor α ameliorates perfluorododecanoic acid-induced production of reactive oxygen species in rat liver

Involvement of NRF2 in Perfluorooctanoic Acid-Induced Testicular Damage in Male Mice1

Effects of Endocrine Disrupters on Immune Function and Inflammation

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