Shifting Anaerobic to Aerobic Metabolism Stimulates Apoptosis Through Modulation of Redox Balance: Potential Intervention in the Pathogenesis of Postoperative Adhesions  

Oleh:

Fletcher, Nicole M. ; Awonuga, Awoniyi O. ; Neubauer, Bailey R. ; Abusamaan, Mohammed S. ; Saed, Mohammed G. ; Diamond, Michael P. ; Saed, Ghassan M.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 104 no. 04 (Oct. 2015), page 1022–1029.
Topik: Dichloroacetate; Postoperative Adhesions; Oxidative Stress; Apoptosis
Fulltext: F02 v104 n4 p1022 kelik2016.pdf (867.03KB)

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Objective: To compare the effect of shifting anaerobic to aerobic metabolism on key regulators of oxidative stress, including extracellular superoxide dismutase (SOD3), inducible nitric oxide synthase (iNOS), and its product, nitric oxide (NO), as well as mitochondrial potential (??m) and apoptosis in fibroblasts established from normal peritoneum and adhesion tissues. Design: Prospective, experimental study. Setting: University medical center. Patient(s): Fibroblasts established from normal peritoneum and adhesion tissues from the same patients. Intervention(s): Treatment with dichloroacetate (0, 20, 40, and 80 µg/mL, 24 hours). Main Outcome Measure(s): The expression of SOD3, iNOS, and NO levels were measured utilizing real-time reverse transcription–polymerase chain reaction and Greiss assay. The ??m was evaluated by the JC-1 Mitochondrial Membrane Potential Assay. Apoptosis was determined by caspase-3 activity and TUNEL assays. Data were analyzed using SPSS 19.0. Mixed model repeated-measures analysis of variance was used with a Bonferroni correction. Significant interactions were analyzed with independent sample t tests. Result(s): Dichloroacetate increased apoptosis, SOD3 messenger RNA, iNOS messenger RNA, and NO levels in fibroblasts from peritoneum and adhesions. There was enhanced ??m adhesion as compared with normal peritoneal fibroblasts. Creating oxidative stress by exposure by hypoxia markedly increased ??m in fibroblasts from normal peritoneum to levels observed in adhesions; dichloroacetate protected against the effects of hypoxia. Conclusion(s): Anaerobic metabolism and oxidative stress are associated with the development of the adhesion phenotype, which manifests decreased apoptosis. Dichloroacetate induces adhesion fibroblasts to undergo apoptosis via modulation of redox homeostasis. These findings may provide targets for therapeutic treatment for reduction of profibrotic disorders, including postoperative adhesions.

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