The severity of hypoxic changes and oxidative DNA damage in the placenta of early-onset preeclamptic women and fetal growth restriction

Kimura, Chiharu; Watanabe, Kazushi; Iwasaki, Ai; Mori, Toshitaka; Matsushita, Hiroshi; Shinohara, Koichi; Wakatsuki, Akihiko

doi:10.3109/14767058.2012.733766

Cited by 71 publications

(44 citation statements)

References 41 publications

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“…Damage caused by oxidative stress, including changes to DNA and proteins, as well as the mechanisms of DNA repair, appears to play a key role in obstetrical pathologies of placental origin, including PE and IUGR (Vascotto et al 2007;Takagi et al 2004;Kimura et al 2013;Rossi et al 2013;Tamura et al 2011). In this paper, we also focus our attention on the immunohistochemical expression of APE1/ Ref-1 (APE1).…”

Section: Introductionmentioning

confidence: 99%

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Londero

Orsaria

Marzinotto

et al. 2016

Histochem Cell Biol

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To evaluate the expression of markers correlated with cellular senescence and DNA damage (8-hydroxy-2′-deoxy-guanosine (8-OHdG), p53, p21, APE1/Ref-1 (APE1), interleukin (IL-6 and IL-8) in placentas from healthy and pathologic pregnancies. This retrospective study considered a placental tissue micro-array containing 92 controls from different gestational ages and 158 pathological cases including preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes,low platelet count), small for gestational age (SGA)fetuses, and intrauterine growth restriction (IUGR) occurringat different gestational ages. In this study, we demonstrated a significant influence of gestational age on the expression in the trophoblast of 8-OHdG, p53, p21, APE1, and IL-6. In placentas of cases affected by PE, HELLP, or IUGR, there was an increased expression of 8-OHdG, p53, APE1, and IL-6 compared to controls (only IL-8 was significantly decreased in cases). In both groups of pathology between 22- and 34-week gestation and after 34-week gestation, APE1 levels were higher in the trophoblast of women affected by hypertensive disorders of pregnancy than women carrying an IUGR fetus. The cytoplasmic expression of 8-OHdG was increased in placentas in IUGR cases compared to PE or HELLP pregnancies. In cases after 34-week gestation, p21 was higher in SGA and IUGR than in controls and late PE. Moreover, p53 was increased after 34-week gestation in IUGR pregnancies. Placentas from pathological pregnancies had an altered expression of\ud 8-OHdG, p53, p21, APE1, IL-6, and IL-8. The alterations of intracellular pathways involving these elements may be the cause or the consequence of placental dysfunction, but in any case reflect an impaired placental function, possibly due to increased aging velocity in pathologic cases

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Section: Introductionmentioning

confidence: 99%

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Londero

Orsaria

Marzinotto

et al. 2016

Histochem Cell Biol

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“…HIF-1α and 8-OHdG staining in nuclei of the placental trophoblast in early-onset preeclamptic women was significantly greater than in late-onset preeclamptic women. 20) These results indicate that under prolonged preeclamptic conditions in early-onset disease, long-term exposure to preeclamptic conditions impairs uterine artery flow, reduces blood flow to the placenta, causes placental oxidative DNA damage, and ultimately leads to FGR. In the present study, we demonstrated that oxygen free radical production is increased without change of antioxidants in the fetus in preeclamptic women with FGR.…”

Section: Discussionmentioning

confidence: 94%

Oxidative stress in the fetus of preeclamptic women with fetal growth restriction

Watanabe

Iwasaki

Mori

et al. 2013

Hypertens Res Pregnancy

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Aim:The aim of this study was to determine whether oxidative stress occurring in the maternal body also affects the fetus in preeclamptic women with fetal growth restriction (FGR). Methods: We recruited 14 preeclamptic women with FGR, 13 preeclamptic women without FGR, and 10 uncomplicated pregnant women. We measured concentrations of derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals and biological antioxidant potential (BAP) in a umbilical artery and vein. Results: Umbilical artery and vein d-ROM levels were elevated in preeclamptic women with FGR compared to the control group. Umbilical artery d-ROM levels were significantly higher than in the vein in preeclamptic women with FGR, but not in those without FGR. Umbilical artery BAP levels did not change significantly in all three groups. Umbilical arterial blood pH was significantly lower and the partial pressure of carbon dioxide (PaCO 2 ) was significantly higher in preeclamptic women with FGR. Umbilical arterial blood partial pressure of oxygen (PaO 2 ) tended to be lower in preeclamptic women with FGR. Conclusions: These results indicate that oxidative stress occurring in the maternal body also affects the fetus in preeclamptic women with FGR.

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“…If 0% of the cells was stained, the score was 0; 1, <10 was 1, 11-25% was 2; 26-50% was 3, and 51-100% was 4. According to the product of the two variables, the samples were categorized as follows: negative (-), 0-3; mildly positive (+), 4-6; moderately positive (++), 7-9; and strongly positive (+++), [10][11][12].…”

Section: Evaluation Of the 8-ohdg P-src And P-egfr Resultsmentioning

confidence: 99%

“…Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases, including cancer. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA and can be used as a biomarker for oral cancer screening [11]. Therefore, the current study used the immunohistochemistry (IHC) SP method to detect the expressions of 8-OHdG, p-Src, and p-EGFR in TSCC and its adjacent tissues; analyzed their relationships and correlations; and preliminarily explored the mechanism of ROSmediated activation of an EGFR signaling pathway to provide information for further studies on the effectiveness of targeted drug treatments in oral cancer.…”

Section: Introductionmentioning

confidence: 99%

Effect of reactive oxygen species on the ligand-independent activation of EGFR in tongue squamous cell carcinoma

Liang¹,

Yu²,

Qin³

2018

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Objective: To explore the expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), p-Src, and phosphorepidermal growth factor receptor (p-EGFR) and the effect of reactive oxygen species on ligand-independent activation of EGFR in tongue squamous cell carcinoma (TSCC) tissues. Methods:The expressions of 8-OHdG, EGFR, and p-EGFR in carcinoma tissues and carcinoma-adjacent tissues of 40 cases of TSCC were determined immunohistochemically. The correlations between 8-OHdG expression and p-Src and p-EGFR expressions were analyzed.Results: 8-OHdG, p-Src, and p-EGFR were highly expressed in TSCC tissues, with positivity rates of 82.5%, 70%, and 55%, respectively, whereas they were lowly expressed in carcinoma-adjacent tissues, with positivity rates of 17.5%, 12.5%, and 7.5%, respectively. The expressions of 8-OHdG, p-Src, and p-EGFR were significantly higher in carcinoma tissue than in carcinoma-adjacent tissue (P < 0.05), and statistically significant correlations were observed between 8-OHdG expression and p-Src and p-EGFR expressions (P < 0.05). Conclusion:This study preliminarily determined the expression of the reactive oxygen species-Src-EGFR signaling pathway in TSCC, providing clinical evidence for the use of cetuximab in combination with other chemotherapy drugs in the treatment of oral cancer.

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The severity of hypoxic changes and oxidative DNA damage in the placenta of early-onset preeclamptic women and fetal growth restriction

Abstract: Our findings indicate that the severity of hypoxic changes and oxidative DNA damage are greater in the placenta of women with early-onset preeclampsia, and that the prolonged preeclamptic conditions may reduce placental blood flow, ultimately leading to FGR.

Cited by 71 publications

References 41 publications

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Oxidative stress in the fetus of preeclamptic women with fetal growth restriction

Effect of reactive oxygen species on the ligand-independent activation of EGFR in tongue squamous cell carcinoma

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