Regression of Experimentally Induced Endometriosis with a New Selective Cyclooxygenase-2 Enzyme Inhibitor

Kilico, Ismail; Kökçü, Arif; Kefeli, Mehmet; Kandemır, Bedrı

doi:10.1159/000356686

Cited by 12 publications

(13 citation statements)

References 27 publications

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“…The cyclooxygenase (COX-2) enzymes that synthesize prostaglandins are highly expressed in endometriotic glands [11], [95], [96], [97] and their increased expression strongly correlates with pathological abnormalities [98], [99], [100], [101]. However, the contribution of the PF milieu to the observed miRNA changes during endometriosis is not clearly known.…”

Section: Discussionmentioning

confidence: 99%

Redox regulation of microRNAs in endometriosis-associated pain

2017

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Endometriosis is a chronic, painful condition with unknown etiology. A differential expression of microRNAs in the endometriotic tissues from women with endometriosis with pain compared to those without suggested a plausible role for miRNA or epigenetic mechanisms in the etiology of endometriotic pain. The peritoneal milieu is involved in maintenance of endometriotic lesion and nociception. We recently showed the mechanistic role for oxidized-lipoproteins (ox-LDLs) present in peritoneal fluid (PF) in endometriosis and pain. We explored the possibility of ox-LDLs modulating the expression of miRNAs in a manner similar to PF from women with endometriosis. Expression levels of miRNAs and their predicted nociceptive and inflammatory targets were determined in PF and ox-LDL treated human endometrial cell-lines. Samples from IRB-approved and consented patients with and without endometriosis or pain were used. These were compared to endometrial cell-lines treated with various forms of oxidized-lipoproteins. RNA (including miRNAs) were isolated from treated endometrial cells and expression levels were determined using commercial miRNome arrays. Cell lysates were used in immunoblotting for inflammatory proteins using a protein array. Twenty miRNAs including isoforms of miR-29, miR-181 and let-7 were mutually differentially expressed in cells treated with PF from endometriosis patients with pain and those treated with ox-LDL components. The ox-LDLs and endo-PF treatment also produced significant overexpression of microRNA predicted target genes nerve growth factor, interleukin-6 and prostaglandin E synthase and overexpression of their downstream protein targets Mip1α and MCP1. This study showed similarities between miRNA regulation in PF from endometriotic women and ox-LDLs present in abundance in the PF of these women. Key miRNAs responsible for targeting nociceptive and inflammatory molecules were downregulated in the presence of ox-LDLs and endo-PF, thus playing a role in the etiology of endometriotic pain. These redox-sensitive miRNAs can be of potential use as targets in the treatment of endometriosis-associated pain.

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Section: Discussionmentioning

confidence: 99%

Redox regulation of microRNAs in endometriosis-associated pain

2017

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“…Previous studies that evaluated histologic changes in endometriosis used GT and ST scoring systems [25][26][27]. Among previous rat endometriosis models that used these scoring systems, imiquimod, interferon-α-2b and dexketoprofen reduced both GT and ST scores significantly, but anastrozole and raloxifene only reduced GT scores [25,27,28].…”

Section: Discussionmentioning

confidence: 99%

“…Among previous rat endometriosis models that used these scoring systems, imiquimod, interferon-α-2b and dexketoprofen reduced both GT and ST scores significantly, but anastrozole and raloxifene only reduced GT scores [25,27,28]. By using these scoring systems, we compared pre-and post-treatment changes in the density of GT and ST, which are main components of endometrial tissue.…”

Section: Discussionmentioning

confidence: 99%

The Non-Ergot Derived Dopamine Agonist Quinagolide as an Anti-Endometriotic Agent

Akyol¹,

Kavak²,

Akyol

et al. 2016

Gynecol Obstet Invest

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Aim: The study aimed to investigate the efficacy of a dopamine agonist, quinagolide, on experimentally induced endometriosis in a rat model. Methods: Twenty female Wistar rats were used in this experiment. Endometriosis was surgically induced by transplantation of autologous endometrial tissue. A second laparotomy was performed 4 weeks after the first one to assess the pre-treatment implant volumes, and peritoneal lavage with saline solution was performed to assess the peritoneal cytokine levels. Rats were randomized to treatment with quinagolide or saline. At the end of the treatment period, a third laparotomy was performed to compare pre- and post-treatment implant volumes and cytokine levels within the groups. Implants were excised to compare glandular tissue (GT) and stromal tissue (ST) scores between the groups. Results: In the quinagolide group, post-treatment volume was statistically significantly reduced compared with pre-treatment volume (p = 0.01). There were significant decreases in interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels in peritoneal fluid samples in quinagolide-treated rats when compared to pre-treatment levels (p = 0.03 and p < 0.01). Histopathologically, both GT and ST scores were significantly lower in the quinagolide group compared to the control group (p = 0.01 and p = 0.02). Conclusions: Quinagolide caused a significant regression in endometriotic implants and it also significantly reduced the levels of IL-6 and VEGF in peritoneal fluid.

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“…The volume of endometriotic lesions was calculated using prolate ellipsoid formula: V(mm 3 ) = 0.52 × length × width ×height (all in millimeters) [17,18,19]. …”

Section: Methodsmentioning

confidence: 99%

Human Chorionic Gonadotropin Improves Endometriosis Through Downregulation of Leptin Expression in Rats

Pang

Yin

et al. 2015

Gynecol Obstet Invest

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Objective: To investigate whether and how human chorionic gonadotropin (HCG) treatment ameliorates endometriosis in an endometriotic rat model. Methods: Twenty-four endometriosis rats were established and were randomly divided into four groups, and then the rats were treated with 19.4, 25.8, and 51.6 IU/100 g weight/day of HCG, respectively. The control group was treated with 0.9% NaCl. After 15 days (3 estrous cycles), the ectopic lesion volume and the expression of leptin protein in eutopic and ectopic endometrium were investigated. Results: After HCG treatment, the volumes of endometriotic lesions were significantly smaller than those before treatment. During endometriosis development, the expression of leptin protein in eutopic and ectopic endometrium was remarkably increased. HCG administration reversed leptin upregulation in endometriotic tissues. Conclusion: HCG therapy appears to be an effective treatment for endometriosis in rats through down-regulation of leptin expression in eutopic and ectopic endometrium.

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Regression of Experimentally Induced Endometriosis with a New Selective Cyclooxygenase-2 Enzyme Inhibitor

Cited by 12 publications

References 27 publications

Redox regulation of microRNAs in endometriosis-associated pain

Redox regulation of microRNAs in endometriosis-associated pain

The Non-Ergot Derived Dopamine Agonist Quinagolide as an Anti-Endometriotic Agent

Human Chorionic Gonadotropin Improves Endometriosis Through Downregulation of Leptin Expression in Rats

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