Browsing by Author "Micili, SC"

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    Lipoic acid decreases peritoneal adhesion formation in a rat uterine scar model
    Micili, SC; Göker, A; Sayin, O; Akokay, P; Ergür, BU
    Objective: To investigate the effects of lipoic acid in the prevention of postoperative pelvic adhesions by a visual scoring system and immunohistochemistry in a rat uterine horn model with full thickness injury. Material and Methods: Twenty-eight female Wistar albino rats were randomised into four groups: uterine trauma control, 15 days and 30 days, and uterine trauma + lipoic acid, 15 days and 30 days. A full thickness defect was established by incising a segment of approximately 1.0 cm in length from each uterine horn, leaving the mesometrium intact. Extension and severity of the adhesions in each group were scored by a visual scoring system and evaluated immunohistochemically. Results: Adhesion scores were 2.00 +/- 0.81, 2.14 +/- 0.69 0.71 +/- 0.75, and 0.85 +/- 0.69 for extent and 2.28 +/- 0.48, 2.14 +/- 0.69, 0.85 +/- 0.69, and 1.14 +/- 0.69 for severity in Groups 1, 2, 3 and 4, respectively. Adhesion extent and severity were significantly less for groups treated by lipoic acid but no difference was observed between long and short administration. Both Vitronectin and u-PAR staining were significantly increased in treatment groups when compared to the control group. Conclusion: Lipoic acid was found to be effective in reducing postoperative adhesion formation in a rat model.
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    The role of resveratrol on full - Thickness uterine wound healing in rats
    Sayin, O; Micili, SC; Goker, A; Kamaci, G; Ergur, BU; Yilmaz, O; Akdogan, GG
    Objective: Healing of the uterus after cesarean section and myomectomy operation is clinically important. In this study, we aimed to investigate the effects of resveratrol (3,5,4'-o-trihydroxystilbene) on the wound healing process of the uterus in rats treated with resveratrol following full thickness injury of the uterus. Materials and methods: Twenty-one female wistar albino rats were divided randomly into three groups (1) control group with no intervention (2) injury group with uterine full thickness injury (3) resveratrol group with uterine full thickness injury and treated with resveratrol. Resveratrol was injected by oral gavage at the doses of 0.5 mg/kg/day for 30 days following uterine full thickness injury. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) distributions were assessed using the immunohistochemical methods in tissue and ELISA methods in the tissue homogenate. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated with colorimetric method and malondialdehyde (MDA) levels also were measured using high performance liquid chromatography in the tissue homogenate. The effects of resveratrol on the uterine histology also were evaluated histologically with the light microscopy. Results: Histological evaluation and immunohistochemical evaluations showed that treatment with a resveratrol significantly increased the thickness of the uterine wall and VEGF expression and decreased expression PDGF during wound healing. Biochemically, GPx and SOD activities were increased significantly after treatment with resveratrol. Additionally, resveratrol administration decreased MDA levels. Conclusion: These results showed that the antioxidant effects of resveratrol has been shown to have a positive influence on wound healing of the uterus. (C) 2017 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V.
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    α-Lipoic Acid Vaginal Administration Contrasts Inflammation and Preterm Delivery in Rats
    Micili, SC; Goker, A; Kuscu, K; Ergur, BU; Fuso, A
    alpha-Lipoic acid (ALA) is a safe natural molecule involved in the immunomodulation of many physiological processes. Orally administered ALA has been reported to treat several inflammatory pathologies and support pregnancy. Our study aimed at testing ALA vaginal administration in female Wistar rats evaluating its tissue distribution (experiment I), impact on implantation process (experiment II), and effectiveness in contrasting induced preterm birth (experiment III). In experiment I, rats were intravaginally treated with 50 mg/kg or 500 mg/kg ALA, or with a physiologic solution, for 4 days. alpha-Lipoic acid distribution in uterus and cervical tissues was evaluated by immunohistochemical analyses. In experiment II, rats received intravaginally the above treatments for 5 days, then they were mated and, if pregnant, included in the experiment to evaluate both implantation rate and the content of implantation mediators in uterus tissues. In experiment III, pregnant rats were pretreated with placebo or with vaginal ALA for 4 days and then induced to delivery with mifepristone plus PGE2 on the 19th day of pregnancy. The delivery time was recorded, and the messenger RNA (mRNA) levels of pro-inflammatory cytokines were detected in the uterine tissues by real-time polymerase chain reaction. Immunohistochemistry was also performed. Results showed that vaginal ALA was well absorbed and distributed. The treatment did not affect the implantation process and was able to significantly revert mifepristone plus prostaglandin E2 effects, delaying the timing of delivery and significantly decreasing mRNA synthesis and release of pro-inflammatory cytokines. We provide for the first time new information on vaginal ALA use, even during pregnancy, opening a perspective for further studies.
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    Protective effect of alpha lipoic acid on 4-vinylcyclohexene diepoxide induced primary ovarian failure in female rats
    Özel, F; Kiray, M; Göker, A; Aydemir, S; Micili, SC
    Objective: The effects of alpha lipoic acid (ALA) and its possible mechanisms in treating Primary ovarian failure (POF) model was studied with 4 vinylcyclohexene diepoxide (VCD). Material and methods: Rats were divided into 4 groups (n = 7) as Control, VCD, VCD + ALA and ALA. POF model was induced by applying VCD intraperitoneally and ALA was administered by oral gavage as 100 mg/day to the VCD + ALA and ALA groups. Results: At the end of 42 days, ovarian and uterine tissues were received. The number of primordial and primary follicles were increased and corpus luteum and cystic follicles were decreased in ovarian tissues in VCD + ALA group compared to VCD group. Caspase-3 immunoreactivity in follicular cells was decreased in VCD + ALA group compared to VCD group. eNOS immunoreactivity and eNOS levels were decreased in VCD group and increased in VCD + ALA group while iNOS immunoreactivity and iNOS levels were increased in VCD group, decreased in VCD + ALA group in ovary and uterine tissue. Plasma FSH and LH hormone levels were increased in the VCD but decreased in VCD + ALA group. Estradiol level decreased in the VCD group compared to the other groups. The MDA values were significantly increased in the VCD + ALA group compared to VCD group. In addition, the levels of GSH values were decreased in VCD + ALA group compared to VCD group. Conclusion: Alpha lipoic acid treatment of rats with VCD-induced POF had a beneficial effect on reducing ovarian damage by improving histological, immunohistochemical, hormone level and oxidative stress markers. Our results show that ALA is an effective treatment of VCD-induced POF rats. (C) 2020 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V.
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    The Role of Proteins in Apoptosis of Somatic and Germ Cells in the Mouse Ovary
    Micili, SC; Vatansever, S; Ozbilgin, K
    In this study, to determine the mechanisms of cell death in developing follicles, we investigated whether expression of Bcl-2, p53 and Bax play a role throughout the growth of follicles in the mice. Ovarian tissues and oocytes were obtained from 30 Mus Musculus type mouse. The immunostaining of ovarian tissue sections and oocytes was performed using anti-Bcl-2, anti-Bax and anti-p53 antibodies and terminal deoxynucleotidyl transfrase (TdT) assay (TUNEL) were also used for detection of internucleosomal DNA fragmentation. In ovarian tissue section evaluation, granulosa cells in antrum of secondary and Graaf follicles were positive with TUNEL staining. Immunoreactivity of Bcl-2 was moderate in primary and secondary follicles of granulosa cells. While immunostaining of p53 was moderate in granulosa cells of Graaf follicles, Bax immunoreactivity was moderate and strong in secondary and Graaf follicles, respectively. When granulosa cells were break off from zona pellucida, there were TUNEL positive cells. In unfertilised oocytes evaluation, TUNEL positive cells were observed in the granulosa cells which were free from zona pellucida. When the granulosa cells were attached with zona pellucida, they were TUNEL negative. While immunoreactivity of Bcl-2 was detected in both oocytes and granulosa cells which were attached with zona pellucida, immunostaining of p53 were only detected in granulosa cells which break off from zona pellucida. In conclusion, regulation of apoptosis in granulosa cells may be controlled by Bax expression and when the granulosa cells were not attached with zona pellucida, they may go into the apoptotic cascade. Therefore; we suggest that, the death of granulosa cells may control signals from intrinsic pathways in the Graaf follicule or from extrinsic pathways after ovulation. However, we consider of further studies to be necessary.
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    Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage
    Monastra, G; De Grazia, S; Micili, SC; Goker, A; Unfer, V
    Introduction: Alpha lipoic acid (ALA) is an essential mitochondrial co-factor and, as a free molecule, it can exert multi-level immunomodulatory functions. Both ALA and its reduced form, dihydrolipoic acid (DHLA), are believed to be able to chelate heavy metals, to regenerate essential antioxidants and to repair important molecules damaged by oxidation. The largest part of the effects of ALA/DHLA couple can be explained by a specific stimulatory activity on Nrf2-dependent gene transcription and by the inhibition of NF-kappa B activity. These features have prompted its use as a drug for several diseases. Areas covered: This article surveys the main features of ALA/DHLA and its therapeutic effects. Its complex and differentiated function cannot simply be reduced to anti-inflammatory, antioxidant and detoxifying action. We highlight its capability to finely modulate several physiological pathways when unbalanced. In particular, we focus our attention on pregnancy, in relation to ALA administration by oral route and by a new formulation for vaginal delivery, in patients with threatened miscarriage. Expert opinion: Future efforts should be devoted to explaining carefully ALA/DHLA mechanism of action to reactivate the physiological balance when modified during pregnancy. On the other hand, ALA safety in pregnant women and its pharmacokinetics by vaginal route, have to be studied in depth. Moreover, ALA efficacy has to be confirmed in a much larger sample of patients.
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    Evaluation of the effects of gonadotropin-relasing hormone antagonist (GnRH-ant) and agonist (GnRH-a) in the prevention of postoperative adhesion formation in a rat model with immunohistochemical analysis
    Tamay, AG; Guvenal, T; Micili, SC; Yildirim, Y; Ozogul, C; Koyuncu, FM; Koltan, SO
    Objective: To investigate the effects of GnRH antagonist (GnRH-ant) and agonist (GnRH-a) in the prevention of postoperative pelvic adhesions by a visual scoring system and immunohistochemical methods in a rat uterine horn model. Design: Controlled experimental animal study. Setting: Animal laboratory at an academic research environment. Animal(s): Twenty-one Wistar albino rats. Intervention(s): Rats were randomized into three groups. One week before the operation the rats received either GnRH-ant or GnRH-a or saline solution; they then underwent surgical laparotomy, and both uterine horns were traumatized by a scalpel. Three weeks later, all rats were sacrificed and extension and severity of the adhesions in each group were scored by a visual scoring system. Adhesion tissues were evaluated immunohistochemically for vitronectin and u-PAR. Main Outcome Measure(s): Scores of extend and severity of adhesions and staining of vitronectin and u-PAR. Result(s): The extent of adhesion scores were 1.85 +/- 0.86, 0.78 +/- 1.05, and 0.42 +/- 0.64, and the severity of adhesion scores were 1.71 +/- 0.91, 0.57 +/- 0.85, 0.50 +/- 0.75 for control, GnRH-ant, and GnRH-a groups, respectively. The extent and severity of adhesions were significantly lower in both GnRH-ant and GnRH-a groups when compared with the control group. Adhesion extent scores in the GnRH-a group were lower than in the GnRHant group, but this difference was not significant. vitronectin and u-PAR staining were significantly greater in both the GnRH-ant and GnRH-a groups than in the control group. Conclusion(s): GnRH-ant as well as GnRH-a reduced postoperative adhesion formation in a rat model. This finding was supported immunohistochemically by vitronectin and u-PAR staining. (Fertil Steril (R) 2011; 96: 1230-3. (C) 2011 by American Society for Reproductive Medicine.)
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    Immunohistochemical and ultrastructural analysis of the effect of omega-3 on embryonic implantation in an experimental mouse model
    Sarsmaz, K; Goker, A; Micili, SC; Ergur, BU; Kuscu, NK
    Objective: Implantation is the first step to a healthy pregnancy. Omega-3 supplementation is common to use during pregnancy, for its antioxidant and membrane stabilising effect. In this study we have aimed to study the effect of Omega-3 supplementation on implantation in a mouse model by immunohistochemical methods and electron microscopic evaluation. Materials and methods: Mice were randomized into three groups to receive standard food, Omega-3 400 mg/kg and Omega-3 1000 mg/kg one menstrual cycle before mating. Mice were sacrificed on third day of estimated implantation and uterine horns were evaluated immunohistochemically for staining of Laminin and Leukemia Inhibitory Factor (LIF) and ultrastructural morphology. Results: Laminin and LIF immunoreactivity were increased signifcantly in the high dose group when compared to the control and low-dose groups in lumen epithelium basal membrane, gland epithelium basal membrane and endometrial stroma. Electron-microscopic evaluation showed a decrease in epithelial height and microvilli loss in the high dose groups. Conclusion: Omega-3 supplementation increased implantation markers Laminin and LIF and decreased epithelial height and microvilli thus seems to prepare the endometrium for a favorable environment of implantation. Copyright (C) 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC.
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    The effect of lipoic acid on wound healing in a full thickness uterine injury model in rats
    Micili, SC; Goker, A; Sayin, O; Akokay, P; Ergur, BU
    Aim of this study was to investigate the effects of lipoic acid on uterine wound healing by immunohistochemical and biochemical assay in a rat uterine horn model with full thickness injury. Thirty-two female Wistar albino rats were randomised into five groups: Control group, with no intervention; uterine scar group 15days (US15d), uterine scar group 15 days + alpha lipoic acid (ALA) (US15d + ALA), uterine scar group 30 days (US30d) and uterine scar group 30 days + ALA (US30 days + ALA). After uterine incision 100 mg/kg of ALA was administered by oral gavage for either 15 or 30 days. Vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (alpha-SMA) distribution were evaluated by immunohistochemical methods in tissue and ELISA methods in tissue homogenate. The percentage of alpha-SMA positive area in US15d + ALA and US30d + ALA groups was significantly higher than US15 and US30d groups. The percentage of VEGF positive area in US15d + ALA group was significantly higher than US15d group and US30d + ALA group was significantly higher than US30d group. Biochemically, alpha-SMA was significantly higher in the US15d + ALA group when compared to US15d group and higher in US30d + ALA group when compared to US30d group. VEGF was significantly higher in US15d + ALA and US30d + ALA groups when compared to US15 and US30d groups. In conclusion, ALA was found to be effective in enhancing wound healing in uterine full thickness injury.
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