The aromatase inhibitor letrozole reduces adhesion formation after intraperitoneal surgery in a rat uterine horn model

Keskin, Hüseyin Levent; Şirin, Yusuf Sinan; Keleş, Hikmet; Turgut, Olcay; İde, Tayfun; Avşar, Ayşe Filiz

doi:10.1016/j.ejogrb.2012.12.002

Cited by 14 publications

(10 citation statements)

References 32 publications

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“…Middle‐aged animals (15 months old) were treated for 14 days with a daily subcutaneous injection of either letrozole, at a dose of 1 mg/kg (LET; Letrozole L6545, Sigma‐Aldrich Chemie, Darmstadt, Germany) or an olive oil vehicle (CTRL; Olivae Oleum Raffinatum, Galvex, Banská Bystrica, Slovak Republic). The dose of the letrozole treatment was chosen according to previously published data . Rats were divided into groups according to sex and randomized to the applied treatment: males and females receiving vehicle (males CTRL, n=14; females CTRL, n=10) or letrozole (males LET, n=12; females LET, n=10).…”

Section: Methodsmentioning

confidence: 99%

Sex‐dependent effects of letrozole on anxiety in middle‐aged rats

Borbélyová

Domonkos

Csongová

et al. 2017

Clin Exp Pharma Physio

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Aromatase catalyzes the conversion of testosterone to estradiol and is involved in the physiological effects of sex hormones on brain function. Animal experiments have shown that the aromatase inhibitor, letrozole, can induce anxiety in young ovariectomized females that are used as a model of aging. Whether or not these effects would be similar in intact middle-aged animals is unknown. The aim of our study was to analyze the effects of letrozole on anxiety in middle-aged rats of both sexes. Fifteen month old male and female rats were treated daily with either letrozole or vehicle for 2 weeks. The elevated plus maze was used to test anxiety-like behaviour. Sex differences were found not only in plasma concentrations of testosterone but also in the effects of letrozole treatment on plasma testosterone (P<.05). The interaction between sex and treatment was also proven in locomotor activity (P<.05) and time spent in the open arms of the elevated plus maze (P<.05). Letrozole-treated male rats spent 95% less time in the open arms of the elevated plus maze than the control rats did (P<.05) suggesting an anxiogenic effect of aromatase inhibition. This difference was not found between letrozole-treated and vehicle-treated females. In contrast to previous experiments on young animals, letrozole seems to induce anxiety in male but not in female middle-aged rats. This sex-specific effect might be related to sex differences of oestrogen and androgen signalling in aging brains. These results should be taken into account in clinical applications of letrozole, especially in men.

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Section: Methodsmentioning

confidence: 99%

Sex‐dependent effects of letrozole on anxiety in middle‐aged rats

Borbélyová

Domonkos

Csongová

et al. 2017

Clin Exp Pharma Physio

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“…Estrogen also regulates angiogenesis and regulation of mesothelial cell proliferation. Therefore, many animal studies have demonstrated that anti-estrogenic agents decreased adhesion formation [6][7][8][35][36][37][38]. In the current study, fulvestrant and micronized progesterone antagonized all these pathways and contributed to the prevention of adhesion formation by creating a hypoestrogenic milieu.…”

Section: Discussionmentioning

confidence: 62%

“…Hypoestrogenic milieu was found to reduce estrogen dependent angiogenic growth factors, epidermal growth factor and platelet derived growth factor caused fibrovascular bands [7]. Therefore, anti-estrogenic drugs may have anti-inflammatory effects which may make their usage possible in the prevention of post-operative adhesion formation [6][7][8]. Fulvestrant, which works as a selective estrogen receptor down-regulator (SERD) is an estrogen receptor antagonist [9].…”

Section: Introductionmentioning

confidence: 97%

“…The balance of inflammation and wound healing process are mediated by the hormones and growth factors. Estrogen also may modulate the expression of vascular endothelial growth factor and basic fibroblast growth factor which leads to expansion of capillary perfusion of adhesion [6]. Hypoestrogenic milieu was found to reduce estrogen dependent angiogenic growth factors, epidermal growth factor and platelet derived growth factor caused fibrovascular bands [7].…”

Section: Introductionmentioning

confidence: 98%

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Evaluation of the effects of fulvestrant and micronized progesterone on the post-operative adhesion formation and ovarian reserve in rat model with immunohistochemical and biochemical analysis

Öner

Ulug

Demirci³

et al. 2015

Gynecological Endocrinology

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“…Rodent models are an established experimental setting in order to simulate human adhesion formation [18,22]. Aim of this study was to show the influence of icodextrin on tissue response, adhesion formation and wound healing, of the parietal and visceral fraction in a rat model.…”

Section: Discussionmentioning

confidence: 99%

Influence of 4% icodextrin solution on peritoneal tissue response and adhesion formation

et al. 2013

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BackgroundPostoperative peritoneal adhesion formation following abdominal surgery remains a relevant surgical problem. The application of soluble physico-chemical barriers like 4% icodextrin is one approach to protect the peritoneal surface from getting linked to adhesive scar. The aim of this study was to investigate the influence of 4% icodextrin on peritoneal tissue response both of visceral and parietal peritoneum, adhesion formation and wound healing.Methods40 rats were divided into two groups. After creation of an intraabdominal defect, either 4% icodextrin (Adept®) or sodium chloride was applied. Animals were sacrificed after 7 and 21 days. Adhesions were scored by an adhesion score. Furthermore, immunohistochemical investigations were conducted to determine the discrete influence of icodextrin on the parietal and visceral peritoneal tissue responses (CD68+ macrophages, CD3+ T-lymphocytes, vimentin for mesenchymal cells, HBME-1 for mesothelial cells, and as components of wound healing COX-2, C-myc, catenin).ResultsPostoperative peritoneal adhesions were predominantly present in the sodium chloride group as compared to the icodextrin group (14/19 (74%) vs. 9/19 (47%); p = 0.048). The adhesion score however did not reveal any significant differences, (p = 0.614). Furthermore, the expression of vimentin in both the parietal and visceral peritoneum after 21 days was significantly lower in the icodextrin group than in the sodium chloride group (p = 0.038 and p = 0.028, respectively). No significant differences were observed for macrophages, lymphocytes, reperitonealisation or the expression of COX-2, C-myc or Catenin.ConclusionsThe intraperitoneal application of 4% icodextrin reduces adhesion formation in comparison to sodium chloride. 4% icodextrin solution reduces the inflammatory and mesenchymal infiltrate in the wounded area, thus improving the ratio of mesothel cells to mesenchymal infiltrate. As demonstrated, icodextrin is able to ameliorate the local tissue response. Further experimental studies would be done to elaborate the impact on the early response of the adaptive immune system, which may then trigger the subsequent wound healing and tissue repair.

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The aromatase inhibitor letrozole reduces adhesion formation after intraperitoneal surgery in a rat uterine horn model

Cited by 14 publications

References 32 publications

Sex‐dependent effects of letrozole on anxiety in middle‐aged rats

Sex‐dependent effects of letrozole on anxiety in middle‐aged rats

Evaluation of the effects of fulvestrant and micronized progesterone on the post-operative adhesion formation and ovarian reserve in rat model with immunohistochemical and biochemical analysis

Influence of 4% icodextrin solution on peritoneal tissue response and adhesion formation

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