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Begum MIA, Chuan L, Hong ST, Chae HS. The Pathological Role of miRNAs in Endometriosis. Biomedicines 2023; 11:3087. [PMID: 38002087 PMCID: PMC10669455 DOI: 10.3390/biomedicines11113087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 11/13/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023] Open
Abstract
Association studies investigating miRNA in relation to diseases have consistently shown significant alterations in miRNA expression, particularly within inflammatory pathways, where they regulate inflammatory cytokines, transcription factors (such as NF-κB, STAT3, HIF1α), and inflammatory proteins (including COX-2 and iNOS). Given that endometriosis (EMS) is characterized as an inflammatory disease, albeit one influenced by estrogen levels, it is natural to speculate about the connection between EMS and miRNA. Recent research has indeed confirmed alterations in the expression levels of numerous microRNAs (miRNAs) in both endometriotic lesions and the eutopic endometrium of women with EMS, when compared to healthy controls. The undeniable association of miRNAs with EMS hints at the emergence of a new era in the study of miRNA in the context of EMS. This article reviews the advancements made in understanding the pathological role of miRNA in EMS and its association with EMS-associated infertility. These findings contribute to the ongoing pursuit of developing miRNA-based therapeutics and diagnostic markers for EMS.
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Affiliation(s)
- Mst Ismat Ara Begum
- Department of Biomedical Sciences, Institute for Medical Science, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea; (M.I.A.B.); (L.C.)
| | - Lin Chuan
- Department of Biomedical Sciences, Institute for Medical Science, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea; (M.I.A.B.); (L.C.)
| | - Seong-Tshool Hong
- Department of Biomedical Sciences, Institute for Medical Science, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea; (M.I.A.B.); (L.C.)
| | - Hee-Suk Chae
- Department of Obstetrics and Gynecology, Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
- Biomedical Research Institute, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea
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Sudirman T, Hatta M, Prihantono P, Bukhari A, Tedjasaputra TR, Lie H. Vitamin E administration as preventive measures for peritoneal/intra-abdominal adhesions: A systematic review and meta-analysis. Ann Med Surg (Lond) 2022; 80:104225. [PMID: 36045847 PMCID: PMC9422189 DOI: 10.1016/j.amsu.2022.104225] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/16/2022] [Accepted: 07/20/2022] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND Peritoneal adhesion still becoming a common complication after abdominal surgeries and become a significant threat to digestive surgeons nowadays. Vitamin E might offer benefits for preventing peritoneal adhesions because of its antioxidant, anti-inflammatory, and anti-fibroblastic properties. This study sought to analyze the relationship between vitamin E administration and peritoneal/intra-abdominal adhesions in rat models. METHODS Potential articles were searched by using specific keywords on Scopus, PubMed, PMC, and Cochrane Library databases until March 12th, 2022. All published studies on vitamin E and peritoneal/abdominal adhesions in rat models were collected. Statistical analysis was performed by using Review Manager 5.4 software. RESULTS A total of 9 studies were included in the final analysis. Pooled analysis of the evidences yielded an association between vitamin E and decreased incidence of substantial peritoneal/intra-abdominal adhesions (RR 0.46; 95%CI: 0.33-0.64, p < 0.00001, I 2 = 61%, random-effect modeling); and reduction in the mean grade of adhesions (Mean Difference -1.53; 95%CI: -2.00, -1.06, p < 0.00001, I 2 = 98%, random-effect modeling). CONCLUSIONS This study proposes that vitamin E supplementation might offer benefits in the prevention of peritoneal/intra-abdominal adhesions. More in-vivo studies with larger sample sizes and proper methods are still needed to confirm the results of our study. If possible, studies on humans might also be warranted.
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Affiliation(s)
- Taufik Sudirman
- Department of Surgery, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia
| | - Mochammad Hatta
- Department of Molecular Biology and Immunology for Infectious Disease, Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia
| | - Prihantono Prihantono
- Department of Surgery, Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia
| | - Agussalim Bukhari
- Department of Nutritional Sciences, Faculty of Medicine, Universitas Hasanuddin, Indonesia
| | - Tjahyadi Robert Tedjasaputra
- Division of Gastroenterology, Department of Internal Medicine, Siloam Hospital Lippo Village, Tangerang, Indonesia
| | - Hendry Lie
- Department of Surgery, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia
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Eren EC, Basım P. Role of peripheral inflammatory biomarkers, transforming growth factor-beta and interleukin 6 in predicting peritoneal adhesions following repeat cesarean delivery. Ir J Med Sci 2022; 191:2697-2704. [PMID: 34988860 DOI: 10.1007/s11845-021-02878-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 11/30/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Repeat cesarean deliveries (CDs) pose a risk in the development of intra-abdominal adhesions. AIM We aimed to examine the incidence and severity of adhesions in repeat CDs using a specific scoring system and assess the predictive power of the pre-operative value of transforming growth factor (TGF)-β and interleukin (IL)-6 with selected peripheral inflammatory biomarkers (PIBs) in the prediction of adhesion formation. METHODS This prospective study enrolled 91 pregnant women at term, who had previously undergone at least one or more scheduled CDs. PIBs, namely C-reactive protein, white blood cell count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index, TGF-β, and IL-6 were studied according to the presence and location of adhesions. RESULTS There was a significant difference only in the variables of the number of CDs, post-operative adhesion index (PAI) score, IL-6, and TGF-β on the presence of adhesion (p < 0.05). The linear regression model revealed that the effect of the number of CDs, PAI score, and IL-6 values on TGF-β was significant (p < 0.05). The effect of the PAI score on TGF-β was higher than that of IL-6. As a reciprocal relationship, the effect of the TGF-β value on the PAI score was also higher than that of IL-6. CONCLUSION In patients with a history of repeat CDs, the preoperative determination of TGF-β seems to be an important independent predictor of POA. The adverse events due to post-operative adhesion caused by repeat CDs can be overcome by detecting high-risk patients with a comprehensive assessment and individualized intervention integrated into overall patient management.
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Affiliation(s)
- Elif Ciler Eren
- Department of Obstetrics and Gynecology, Medipol University Medical Faculty, Istanbul, Turkey
| | - Pelin Basım
- Department of General Surgery, Medipol University Medical Faculty, Istanbul, Turkey.
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Evaluation of the Therapeutic Effects of the Hydroethanolic Extract of Portulaca oleracea on Surgical-Induced Peritoneal Adhesion. Mediators Inflamm 2021; 2021:8437753. [PMID: 34381307 PMCID: PMC8352699 DOI: 10.1155/2021/8437753] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 07/18/2021] [Indexed: 01/26/2023] Open
Abstract
Objective Peritoneal adhesion (PA) is an abnormal connective tissue that usually occurs between tissues adjacent to damaged organs during processes such as surgery. In this study, the anti-inflammatory and antioxidant effects of Portulaca oleracea (PO) were investigated against postoperative-induced peritoneal adhesion. Methods Thirty healthy male Wistar rats (220 ± 20 g, 6-8 weeks) were randomly divided into four groups: (1) normal, (2) control (induced peritoneal adhesion), and (3) and (4) PO extracts (induced peritoneal adhesion and received 100 or 300 mg/kg/day of PO extract for seven days). Finally, macroscopic and microscopic examinations were performed using different scoring systems and immunoassays in the peritoneal lavage fluid. Results We found that the levels of adhesion scores and interleukin- (IL-) 1β, IL-6, IL-10, tumour necrosis factor- (TNF-) α, transforming growth factor- (TGF-) β 1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were increased in the control group. However, PO extract (100 and 300 mg/kg) notably reduced inflammatory (IL-1β, IL-6, and TNF-α), fibrosis (TGF-β 1), angiogenesis (VEGF), and oxidative (MDA) factors, while increased anti-inflammatory cytokine IL-10, antioxidant factor glutathione (GSH), compared to the control group. Conclusion Oral administration of PO improved postoperational-induced PA by alleviating the oxidative factors, fibrosis, inflammatory cytokines, angiogenesis biomarkers, and stimulating antioxidative factors. Hence, PO can be considered a potential herbal medicine to manage postoperative PA. However, further clinical studies are required to approve the effectiveness of PO.
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Adewuyi EO, Sapkota Y, International Endogene Consortium (IEC), 23andMe Research Team, International Headache Genetics Consortium (IHGC), Auta A, Yoshihara K, Nyegaard M, Griffiths LR, Montgomery GW, Chasman DI, Nyholt DR. Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity. Genes (Basel) 2020; 11:E268. [PMID: 32121467 PMCID: PMC7140889 DOI: 10.3390/genes11030268] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 02/28/2020] [Accepted: 02/28/2020] [Indexed: 01/02/2023] Open
Abstract
Observational epidemiological studies indicate that endometriosis and migraine co-occur within individuals more than expected by chance. However, the aetiology and biological mechanisms underlying their comorbidity remain unknown. Here we examined the relationship between endometriosis and migraine using genome-wide association study (GWAS) data. Single nucleotide polymorphism (SNP) effect concordance analysis found a significant concordance of SNP risk effects across endometriosis and migraine GWAS. Linkage disequilibrium score regression analysis found a positive and highly significant genetic correlation (rG = 0.38, P = 2.30 × 10-25) between endometriosis and migraine. A meta-analysis of endometriosis and migraine GWAS data did not reveal novel genome-wide significant SNPs, and Mendelian randomisation analysis found no evidence for a causal relationship between the two traits. However, gene-based analyses identified two novel loci for migraine. Also, we found significant enrichment of genes nominally associated (Pgene < 0.05) with both traits (Pbinomial-test = 9.83 × 10-6). Combining gene-based p-values across endometriosis and migraine, three genes, two (TRIM32 and SLC35G6) of which are at novel loci, were genome-wide significant. Genes having Pgene < 0.1 for both endometriosis and migraine (Pbinomial-test = 1.85 ×10-°3) were significantly enriched for biological pathways, including interleukin-1 receptor binding, focal adhesion-PI3K-Akt-mTOR-signaling, MAPK and TNF-α signalling. Our findings further confirm the comorbidity of endometriosis and migraine and indicate a non-causal relationship between the two traits, with shared genetically-controlled biological mechanisms underlying the co-occurrence of the two disorders.
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Affiliation(s)
- Emmanuel O. Adewuyi
- School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4000, Australia;
| | - Yadav Sapkota
- Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA;
| | | | | | | | - Asa Auta
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK;
| | - Kosuke Yoshihara
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 950-2181, Japan;
| | - Mette Nyegaard
- Department of Biomedicine – Human Genetics, Aarhus University, DK-8000 Aarhus, Denmark;
- iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, DK-2100 Copenhagen, Denmark
| | - Lyn R. Griffiths
- School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4000, Australia;
| | - Grant W. Montgomery
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia;
| | - Daniel I. Chasman
- Divisions of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA;
| | - Dale R. Nyholt
- School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4000, Australia;
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Karlı P, Demir Dural M, Bıldırcın FD, Özdemir AZ. The Importance of Serum Prolidase Activity in Endometriosis. JOURNAL OF CLINICAL AND EXPERIMENTAL INVESTIGATIONS 2019. [DOI: 10.5799/jcei/5903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Jelodar G, Azimifar A. Evaluation of serum cancer antigen 125, resistin, leptin, homocysteine, and total antioxidant capacity in rat model of endometriosis treated with Curcumin. Physiol Rep 2019; 7:e14016. [PMID: 30806992 PMCID: PMC6383109 DOI: 10.14814/phy2.14016] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 02/01/2019] [Accepted: 02/03/2019] [Indexed: 01/01/2023] Open
Abstract
Endometriosis is one of the most common reproductive diseases of women, with some important biochemical changes in the serum. Curcumin was reported to have anti-endometriosis, anti-inflammatory and antioxidant activity. This study explores the changes of serum levels of Cancer Antigen 125 (CA125), leptin, resistin, homocysteine, and total antioxidant capacity (TAC) in a rat model of endometriosis and the effect of curcumin treatment on these factors. Fifty female Sprague-Dawley rats (220-250 gr body weight) were randomly divided into control (received 0.3 mL of the vehicle), sham(stress of surgery + 0.3 mL of the vehicle) and three endometriosis groups as danazol treatment (7.2 mg/kg BW, IP), curcumin treatment (48 mg/kg BW, IP) and test (received 0.3 mL of the vehicle). Endometriosis was induced by surgically auto-transplantation of uterine tissue to the abdominal wall and intestinal mesentery. The animals were treated for 4 weeks. On the last day, the blood sample was collected by heart puncture, and the above-mentioned factors were measured in the sera. Leptin in the curcumin treatment group was markedly higher than all of the studied groups, except the danazol group, while there were no significant differences between other groups (P < 0.05). Level of resistin in endometriosis groups did not show significant differences with the control group (P < 0.05). There was no significant difference in the serum levels of homocysteine and CA 125 between all of the studied groups (P > 0.05). The serum levels of TAC in the control group were significantly higher than all of the studied groups (P < 0.05). Curcumin could prevent the growth of endometriosis, while there was no significant alteration on measured factors in the serum of rat with induced endometriosis. Hence follow up of these parameters in serum may not be a proper indicator to evaluate the status of endometriosis in the rat model.
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Affiliation(s)
- Gholamali Jelodar
- Department of Basic ScienceSchool of Veterinary MedicineShiraz UniversityShirazIran
| | - Azimeh Azimifar
- Department of Basic ScienceSchool of Veterinary MedicineShiraz UniversityShirazIran
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Ciebiera M, Włodarczyk M, Zgliczyńska M, Łukaszuk K, Męczekalski B, Kobierzycki C, Łoziński T, Jakiel G. The Role of Tumor Necrosis Factor α in the Biology of Uterine Fibroids and the Related Symptoms. Int J Mol Sci 2018; 19:E3869. [PMID: 30518097 PMCID: PMC6321234 DOI: 10.3390/ijms19123869] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 11/27/2018] [Accepted: 11/28/2018] [Indexed: 12/20/2022] Open
Abstract
Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. The incidence of UFs has been estimated at 25⁻80% depending on selected population. The pathophysiology of UFs remains poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is the main component of all pathways leading to UF tumor formation and tumor necrosis factor α (TNF-α) is believed to be one of the key factors in this field. TNF-α is a cell signaling protein involved in systemic inflammation and is one of the cytokines responsible for the acute phase reaction. This publication presents current data about the role of tumor necrosis factor α in the biology of UFs and the related symptoms. TNF-α is an extremely important cytokine associated with the biology of UFs, UF-related symptoms and complaints. Its concentration has been proven to be elevated in women with clinically symptomatic UFs. The presented data suggest the presence of an "inflammation-like" state in women with UFs where TNF-α is a potent inflammation inducer. The origin of numerous symptoms reported by women with UFs can be traced back to the TNF-α influence. Nevertheless, our knowledge on this subject remains limited and TNF-α dependent pathways in UF pathophysiology should be investigated further.
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Affiliation(s)
- Michał Ciebiera
- Second Department of Obstetrics and Gynecology, The Center of Postgraduate Medical Education, 01-809 Warsaw, Poland.
| | - Marta Włodarczyk
- Department of Biochemistry and Clinical Chemistry, Department of Pharmacogenomics, Medical University of Warsaw, 02-097 Warsaw, Poland.
| | - Magdalena Zgliczyńska
- Students' Scientific Association at the I Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland.
| | - Krzysztof Łukaszuk
- Department of Obstetrics and Gynecological Nursing, Faculty of Health Sciences, Medical University of Gdansk, 80-210 Gdansk, Poland.
- INVICTA Fertility and Reproductive Center, 80-172 Gdansk, Poland.
| | - Błażej Męczekalski
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-513 Poznan, Poland.
| | - Christopher Kobierzycki
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
| | - Tomasz Łoziński
- Department of Obstetrics and Gynecology Pro-Familia Hospital, 35-001 Rzeszów, Poland.
| | - Grzegorz Jakiel
- First Department of Obstetrics and Gynecology, The Center of Postgraduate Medical Education, 01-004 Warsaw, Poland.
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Affiliation(s)
- Roberto Marci
- b Department of Morphology, Surgery and Experimental Medicine , University of Ferrara , Italy
- c Department of Obstetrics and Gynecology , University Hospital of Geneva , Switzerland
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Asghari S, Valizadeh A, Aghebati-Maleki L, Nouri M, Yousefi M. Endometriosis: Perspective, lights, and shadows of etiology. Biomed Pharmacother 2018; 106:163-174. [DOI: 10.1016/j.biopha.2018.06.109] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 05/31/2018] [Accepted: 06/18/2018] [Indexed: 12/24/2022] Open
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Torres K, Pietrzyk Ł, Plewa Z, Załuska-Patel K, Majewski M, Radzikowska E, Torres A. TGF-β and inflammatory blood markers in prediction of intraperitoneal adhesions. Adv Med Sci 2018; 63:220-223. [PMID: 29223125 DOI: 10.1016/j.advms.2017.11.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Revised: 08/11/2017] [Accepted: 11/21/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE Intraperitoneal adhesions (IA) develop as a consequence of the healing process in peritoneum injured during surgeries. IA might be formed after all types of surgical interventions regardless the surgical approach with a higher incidence in obese individuals. Here we determine the diagnostic power of TGF-β and blood inflammatory parameters in the prediction of IA in obese patients undergoing second surgical intervention. MATERIALS AND METHODS Eighty patients were divided into groups according to body mass index (BMI) values and presence of intraperitoneal adhesions (IA). Evaluation of peritoneal adhesion index (PAI), serum TGF-β and blood inflammatory parameters was performed. RESULTS Level of TGF-β, C-reactive protein (CRP), leukocytes, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were significantly higher in obese patients while TGF-β, CRP, and leukocytes were higher in patients with IA. There was a significant correlation between PAI values and TGF-β concentration (p<0.001; r=0.869) in IA group. CONCLUSIONS The preoperative TGF-β concentration, BMI, CRP and NLR could be strong predictors of intraperitoneal adhesions in patients with the history of surgeries.
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Liu Z, Cheng S, Gu C, Pei H, Hong X. Effect of Hydrogen-Rich Saline on Postoperative Intra-Abdominal Adhesion Bands Formation in Mice. Med Sci Monit 2017; 23:5363-5373. [PMID: 29127274 PMCID: PMC5695092 DOI: 10.12659/msm.904669] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background Postsurgical peritoneal adhesions (PPAs) are pathologic fibrous bands within the peritoneal cavity. The aim of this study was to investigate the protective effect of hydrogen-rich saline (HRS) on PPAs formation in mice. Material/Methods Adhesions were induced in mice using the cecum rubbing model. The mice were allocated into 4 groups: control sham group without cecum rubbing; PPA group with saline applied intraperitoneally (i.p.) daily after cecum rubbing; PPA+HRS (5) group with 5 ml/kg of HRS applied i.p. daily after cecum rubbing; and PPA+HRS (10) group with 10 ml/kg of HRS applied i.p. daily after cecum rubbing. On the 1st, 3rd, and 7th days after the operation, mice were killed and pathological adhesion bands were quantified to detect the effect of HRS on PPAs formation. Results HRS did not affect PPAs formation on the 1st day, but did make a significant reduction on the 3rd and 7th days. A significant increase of t-PA and decrease of TGF-β1 and PAI-1 in the peritoneal fluids were observed in the HRS-treated groups. The levels of MDA and MPO in the HRS-treated groups were significantly lower than those in the PPA group. TNF-α and IL-6 levels in HRS-treated groups significantly decreased compared with those in the PPA group on postoperative day 3 and 7. Moreover, HRS decreased the mRNA levels of pro-inflammatory cytokines and TGF-β1 expression in the postsurgical adhesion bands. Conclusions These results showed that HRS had therapeutic potential for preventing PPAs formation, possibly through balancing the expression of TGF-β1, t-PA, and PAI-1, and inhibiting oxidative stress and inflammation.
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Affiliation(s)
- Zhong Liu
- Department of Emergency Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Sanfang Cheng
- Department of Emergency Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Changwei Gu
- Department of Emergency Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Honghong Pei
- Department of Emergency Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Xin Hong
- Department of Emergency Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
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Vignini A, Sabbatinelli J, Clemente N, Delli Carpini G, Tassetti M, Zagaglia G, Ciavattini A. Preperitoneal Fat Thicknesses, Lipid Profile, and Oxidative Status in Women With Uterine Fibroids. Reprod Sci 2017; 24:1419-1425. [PMID: 28122481 DOI: 10.1177/1933719116689598] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE There is growing evidence supporting a possible role for metabolic syndrome and its determinants, such as dyslipidemia, in uterine fibroid (UF) pathogenesis. The present study aims to investigate the association between UFs and visceral and subcutaneous fat thickness (SFT), lipid profile, and oxidative and antioxidative status. METHODS In this cross-sectional study, 35 patients diagnosed with UFs and 15 women without UFs were enrolled. Clinical history and anthropometric parameters were collected for every woman. Characteristics of UFs, preperitoneal fat thickness (PFT), and SFT were assessed ultrasonically. Lipid profile, glucose, thiobarbituric acid reactive substances (TBARs), and superoxide dismutase (SOD) activity were evaluated on plasma from participants. RESULTS Women with UFs showed a significantly increased PFT (11.63 ± 3.39 vs 7.01 ± 3.10 mm; P < .001), lower levels of high-density lipoprotein cholesterol (HDL-C; 45.4 ± 8.3 vs 57.2 ± 13.4 mg/dL; P = .017), higher levels of low-density lipoprotein cholesterol (LDL-C; 92.3 ± 21.5 vs 72.0 ± 14.6 mg/dL; P = .007), and oxidized LDL (65.2 ± 20.7 vs 43.0 ± 11.3 U/L; P = .002). In patients, TBARs concentration was significantly higher (9.41 ± 6.49 vs 2.92 ± 1.65 nmol malondialdehyde/100 μg prot; P < .001), whereas SOD activity was lower (1.09 ± 0.19 vs 1.37 ± 0.41 U/μL; P = .005). Preperitoneal fat thickness was positively associated with body mass index, oxidized LDL, and TBARs. At multivariate analysis, PFT and HDL-C maintained a significant correlation with the diagnosis of UFs. CONCLUSION Chronic inflammation triggered and sustained by visceral fat could play a determinant role in cell differentiation and proliferation processes, necessary for the development of UFs. Alterations in cholesterol fractions may be explained as a consequence of the increased visceral fat deposits and can reflect an increased risk of subclinical atherosclerosis in patients with UF.
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Affiliation(s)
- Arianna Vignini
- 1 Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
| | - Jacopo Sabbatinelli
- 1 Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
| | - Nicolò Clemente
- 2 Woman's Health Sciences Department, Gynecologic Section, Università Politecnica delle Marche, Ancona, Italy
| | - Giovanni Delli Carpini
- 2 Woman's Health Sciences Department, Gynecologic Section, Università Politecnica delle Marche, Ancona, Italy
| | - Marta Tassetti
- 2 Woman's Health Sciences Department, Gynecologic Section, Università Politecnica delle Marche, Ancona, Italy
| | - Giulia Zagaglia
- 2 Woman's Health Sciences Department, Gynecologic Section, Università Politecnica delle Marche, Ancona, Italy
| | - Andrea Ciavattini
- 2 Woman's Health Sciences Department, Gynecologic Section, Università Politecnica delle Marche, Ancona, Italy
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Bi J, Zhang S, Du Z, Zhang J, Deng Y, Liu C, Zhang J. Peripheral serotonin regulates postoperative intra-abdominal adhesion formation in mice. Sci Rep 2017; 7:10001. [PMID: 28855642 PMCID: PMC5577130 DOI: 10.1038/s41598-017-10582-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 08/09/2017] [Indexed: 01/21/2023] Open
Abstract
The aim of the present study is to investigate the role and potential mechanisms of peripheral serotonin in postoperative intra-abdominal adhesion formation in mice. The caecum-rubbing operations were conducted for intra-abdominal adhesion formation modelling in wild-type and Tph1-/- mice. The deficiency of serotonin significantly decreased the adhesion scores, weight loss, and adhesion thickness as well as levels of collagen fibres and hydroxyproline in the adhesive tissues. The Tph1-/- mice exhibited a milder inflammatory response and oxidative stress in the adhesive tissues than did the wild-type mice. Moreover, the deficiency of serotonin reduced the levels of PAI-1 and fibrinogen, and raised the t-PA and t-PA/PAI levels in the peritoneal fluids. Moreover, the expressions of CD34, VEGF, TGF-β and 5-HT2B receptor in the adhesive tissues were significantly decreased in the Tph1-/- group mice. Furthermore, the Tph1-/- +5-HTP group showed more severe adhesions than did the Tph1-/- group mice, and the p-chlorophenylalanine (PCPA) could markedly alleviated the adhesion formation in the WT mice. In conclusion, the present study showed that peripheral serotonin regulated postoperative intra-abdominal adhesion formation by facilitating inflammation, oxidative stress, disorder of the fibrinolytic system, angiopoiesis and TGF-β1 expression via the 5-HT2B receptor in the adhesive tissues.
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Affiliation(s)
- Jianbin Bi
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China
| | - Simin Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China
| | - Zhaoqing Du
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China
| | - Jia Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China
| | - Yan Deng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China
| | - Chang Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China.
- Department of SICU, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China.
| | - Jingyao Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China.
- Department of SICU, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China.
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Fletcher NM, Abusamaan MS, Memaj I, Saed MG, Al-Hendy A, Diamond MP, Saed GM. Oxidative stress: a key regulator of leiomyoma cell survival. Fertil Steril 2017; 107:1387-1394.e1. [PMID: 28483502 DOI: 10.1016/j.fertnstert.2017.04.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 04/10/2017] [Accepted: 04/19/2017] [Indexed: 01/22/2023]
Abstract
OBJECTIVE To determine the effects of attenuating oxidative stress with the use of dichloroacetate (DCA) on the expression of key redox enzymes myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) as well as on apoptosis. DESIGN Prospective experimental study. SETTING University medical center. PATIENT(S) Cells established from myometrium and uterine fibroid from the same patients. INTERVENTION(S) Cells were exposed to normal (20% O2) or hypoxic (2% O2) conditions for 24 hours with or without DCA (20 μg/mL), a metabolic modulator that shifts anaerobic to aerobic metabolism. MAIN OUTCOME MEASURE(S) Nitrate/nitrite (iNOS activity indicator), iNOS, Bcl-2/Bax ratio, MPO, and caspase-3 activities and levels were determined by means of Greiss assay, real-time reverse-transcription polymerase chain reaction, and ELISA. Data were analyzed with the use of SPSS by means of one-way analysis of variance with Tukey post hoc analysis and independent t tests. RESULT(S) MPO, iNOS, and nitrate/nitrite expression were higher in leiomyoma than in myometrial cells, and they were further enhanced by hypoxia in myometrial cells. Treatment with the use of DCA decreased MPO, iNOS, and nitrate/nitrite levels and negated the effect of hypoxia in both types of cells. Leiomyoma cells showed less apoptosis, as indicated by both caspase-3 activity and the Bcl-2/Bax ratio, than myometrial cells. Hypoxia further decreased apoptosis in myometrial cells with no further effect on leiomyoma cells. Treatment with DCA resulted in increased apoptosis in both types of cells, even in the presence of hypoxia. CONCLUSION(S) Shifting anaerobic to aerobic metabolism with the use of DCA resulted in an increase in apoptosis in leiomyoma cells and protected myometrial cells from the acquisition of the leiomyoma-like phenotype.
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Affiliation(s)
- Nicole M Fletcher
- Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan
| | - Mohammed S Abusamaan
- Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan
| | - Ira Memaj
- Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan
| | - Mohammed G Saed
- Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan
| | - Ayman Al-Hendy
- Department of Obstetrics and Gynecology, Augusta University, Augusta, Georgia
| | - Michael P Diamond
- Department of Obstetrics and Gynecology, Augusta University, Augusta, Georgia
| | - Ghassan M Saed
- Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan.
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16
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Wu P, Li F, Zhang J, Yang B, Ji Z, Chen W. Phytochemical compositions of extract from peel of hawthorn fruit, and its antioxidant capacity, cell growth inhibition, and acetylcholinesterase inhibitory activity. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:151. [PMID: 28284186 PMCID: PMC5346202 DOI: 10.1186/s12906-017-1662-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 03/07/2017] [Indexed: 11/10/2022]
Abstract
BACKGROUND Hawthorn fruit (HF) is a well-known traditional medicine in China with the effects of improving digestion and regulating qi-flowing for removing blood stasis. Modern pharmacological experiments showed that HF extract has various pharmaceutical properties and flavonoids are considered as the main bioactive compounds. In this paper, Diaion HP-20 adsorption chromatography was used to enrich flavonoids in PHF, and the phytochemical composition of EPHF was analyzed by high performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS). In addition, EPHF's antioxidant capacity, acetylcholinesterase (AChE) inhibitory activity and cytotoxic activity were evaluated. METHODS EPHF was obtained by Diaion HP-20 adsorption chromatography. Phytochemical composition of EPHF was analyzed qualitatively and quantitatively using HPLC and LC-MS. Radical scavenging capacity of EPHF was estimated using 2,2-diphenyl-1-picryhydrazyl (DPPH) assay and oxygen radical absorbance capacity (ORAC) assay. The AChE inhibitory activity of EPHF was evaluated by Ellman method. Cytotoxic activity of EPHF was assessed by means of MTT assay. RESULTS Eight kinds of components were identified, in which ideain with the value of 179.4 mg/g was identified to be present in the highest level in EPHF, followed by (-)-epicatechin, chlorogenic acid, cyanidin 3-arabinoside, hyperoside and isoquercitrin at the concentrations of 40.9, 10.0, 1.4, 0.4 and 0.2 mg/g, respectively. The contents of these compounds in EPHF were much higher than those in PHF and HF. In addition, EPHF exhibited strong antioxidant and AChE inhibitory activity (ORAC value: 11.65 ± 2.37 μM Trolox equivalents (TE)/mg, DPPH IC50 value: 6.72 μg/mL, anti-AChE activity IC50 value: 11.72 μg/mL) compared with PHF and HF. Moreover, EPHF exhibited high levels of cytotoxicity on MCF-7 and SKOV-3 human tumour cell lines in a dose-dependent manner with the IC50 of 2.76 and 80.11 μg/mL, respectively. CONCLUSIONS Macroporous resin is useful for the extraction and separation of the total flavonoids from PHF. The contents of flavonoids especially anthocyanin in EPHF were increased significantly compared with the PHF, and EPHF exhibited strong antioxidant, AChE inhibitory activity and cytotoxicity on human tumour cells.
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Affiliation(s)
- Panpan Wu
- Anhui University of Chinese Medicine, Hefei, 230012 China
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei Ave., Dongcheng District, Beijing, 100700 China
| | - Fajie Li
- State Key Laboratory of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700 China
- Flow Station of Post-Doctoral Scientific Research, China Academy of Chinese Medical Sciences, Beijing, 100700 China
| | - Jianyong Zhang
- Pharmacy School, Zunyi Medical University, Guizhou, 563000 China
| | - Bin Yang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei Ave., Dongcheng District, Beijing, 100700 China
| | - Zhaojie Ji
- Anhui University of Chinese Medicine, Hefei, 230012 China
| | - Weidong Chen
- Anhui University of Chinese Medicine, Hefei, 230012 China
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17
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Santanam N, Zoneraich N, Parthasarathy S. Myeloperoxidase as a Potential Target in Women With Endometriosis Undergoing IVF. Reprod Sci 2016; 24:619-626. [PMID: 27662901 DOI: 10.1177/1933719116667225] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
As infertility is intimately associated with endometriosis, the levels of myeloperoxidase (MPO), a leukocyte enzyme and an oxidative stress marker, were determined in a case-control prospective study of 68 women with and without endometriosis undergoing in vitro fertilization in the outpatient fertility center within a tertiary care academic medical center. Measured values included plasma and follicular fluid (FF) concentrations of MPO, plasma estradiol, as well as oocyte quality, fertilization, implantation, and pregnancy rates in these women. In FF (mean ± standard error of mean [SEM]), the MPO concentrations (ng/mL) for controls were 4.3 ± 0.37, mild endometriosis (stages I-II) 3.9 ± 0.17, and moderate/severe endometriosis (stages III-IV) 16.6 ± 12.5 ( P < 0.0143). In FF, among patients supplemented with vitamins E and C, the MPO levels decreased significantly only in moderate/severe endometriosis from 25.3 ± 22.0 ng/mL to 4.9 ± 1.61 ng/mL, respectively. Plasma levels of MPO between groups did not change. Outcome data revealed a trend toward decreased percentage of mature oocytes, implantation rate, and clinical pregnancy rate with severity of endometriosis and MPO levels. Myeloperoxidase may be a potential oxidative stress target for endometriosis-associated infertility.
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Affiliation(s)
- Nalini Santanam
- 1 Department of Gynecology & Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.,2 Department of Pharmacology, Physiology & Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Nathaniel Zoneraich
- 1 Department of Gynecology & Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.,3 Advanced Fertility Care, Scottsdale, AZ, USA
| | - Sampath Parthasarathy
- 1 Department of Gynecology & Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.,4 Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA
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18
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Soylu Karapinar O, Pinar N, Özgür T, Özcan O, Bayraktar HS, Kurt RK, Nural O. The Protective Role of Dexpanthenol on the Endometrial Implants in an Experimentally Induced Rat Endometriosis Model. Reprod Sci 2016; 24:285-290. [PMID: 27313118 DOI: 10.1177/1933719116653682] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Dexpanthenol (Dxp), antioxidant and anti-inflammatory agent, plays an important role in the repair systems against oxidative stress and inflammatory response. The objective of this study is to determine the effect of Dxp on experimental endometriosis model. STUDY DESIGN A prospective experimental study was conducted in Experimental Animal Laboratory of Mustafa Kemal University, Hatay. Twenty nonpregnant female Wistar albino rats, in which experimental model of endometriosis was surgically induced, were randomly divided into 2 groups. Group 1 was administered 500 mg/kg/d Dxp intraperitoneally for 14 days, and group 2 was given the same amount of saline solution. After 2 weeks of medication, the rats were killed and implant volumes, histopathologic scores; and levels of serum total antioxidant status, total oxidant status (TOS), and oxidative stress index (OSI) were evaluated. Plasma and peritoneal fluid levels of tumor necrosis factor α (TNF-α) were analyzed. RESULTS The endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values were significantly decreased ( P < .05) in the Dxp group compared to the control group. Plasma and peritoneal fluid TNF-α levels were significantly decreased ( P < .05) in the Dxp group compared to the control group. CONCLUSION Dexpanthenol has free radical scavenger effects, and antioxidant properties has significantly regressed endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values. Serum and peritoneal fluid TNF-α levels were significantly decreased in the Dxp group. So Dxp decreased oxidative stress.
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Affiliation(s)
- Oya Soylu Karapinar
- 1 Department of Obstetrics and Gynaecology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
| | - Neslihan Pinar
- 2 Department of Medical Pharmacology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
| | - Tümay Özgür
- 3 Department of Pathology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
| | - Oğuzhan Özcan
- 4 Department of Biochemistry, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
| | - H Suphi Bayraktar
- 5 Department of Medical Microbiology, Faculty of Medicine, Çukurova University, Adana, Turkey
| | - Raziye Keskin Kurt
- 1 Department of Obstetrics and Gynaecology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
| | - Orhan Nural
- 1 Department of Obstetrics and Gynaecology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
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19
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Güney M, Nasir S, Oral B, Karahan N, Mungan T. Effect of Caffeic Acid Phenethyl Ester on the Regression of Endometrial Explants in an Experimental Rat Model. Reprod Sci 2016; 14:270-9. [PMID: 17636241 DOI: 10.1177/1933719107300911] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The objective of this study is to determine the effects of antioxidant and anti-inflammatory caffeic acid phenethyl ester (CAPE) on experimental endometriosis, peritoneal superoxide dismutase (SOD) and catalase (CAT) activities, and malondialdehyde (MDA) levels in the rat endometriosis model. Thirty rats with experimentally induced endometriosis were randomly divided into 2 groups and treated for 4 weeks with intraperitoneal CAPE (CAPE-treated group; 10 micromol/kg/d, n = 13) or vehicle (control group; n = 13). The volume and weight changes of the implants were calculated. Immunohistochemical and histologic examinations of endometriotic explants by semiquantitative analysis and measurements of peritoneal SOD, CAT, and MDA levels were made. Following 4 weeks of treatment with CAPE, there were significant differences in posttreatment spherical volumes (37.4 +/- 14.7 mm(3) vs 147.5 +/- 41.2 mm(3)) and explant weights (49.1 +/- 28.5 mg vs 158.9 +/- 50.3 mg) between the CAPE-treated groups and controls. The mean evaluation nomogram levels in glandular epithelium for COX-2 positivity by scoring system were 2.1 +/- 0.3 in the CAPE-treated group and 3.9 +/- 0.3 in the control group. In the CAPE-treated group, peritoneal levels of MDA and activities of SOD and CAT significantly decreased when compared with the control group (P < .01). Histologic analysis of the explants demonstrated mostly atrophy and regression in the treatment group, and semiquantitative analysis showed significantly lower scores in rats treated with CAPE compared with the control group. CAPE appeared to cause regression of experimental endometriosis.
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Affiliation(s)
- Mehmet Güney
- Department of Obstetrics and Gynecology, Suleyman Demirel University, Isparta, Turkey.
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20
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Xiong Y, Liu Y, Xiong W, Zhang L, Liu H, Du Y, Li N. Hypoxia-inducible factor 1α-induced epithelial–mesenchymal transition of endometrial epithelial cells may contribute to the development of endometriosis. Hum Reprod 2016; 31:1327-38. [DOI: 10.1093/humrep/dew081] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 03/17/2016] [Indexed: 12/23/2022] Open
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Artis T, Artis AS, Arslan E, Mutlu F, Akay A, Deniz K. Preventive Effect of Ethyl Pyruvate on Postoperative Adhesion Formation Following Abdominal Surgery. J INVEST SURG 2016; 29:260-5. [DOI: 10.3109/08941939.2016.1149639] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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22
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Atta H, El-Rehany M, Roeb E, Abdel-Ghany H, Ramzy M, Gaber S. Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats. Int J Surg 2016; 26:58-63. [PMID: 26790972 DOI: 10.1016/j.ijsu.2015.12.065] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 11/24/2015] [Accepted: 12/07/2015] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Postoperative peritoneal adhesions continue to be a major source of morbidity and occasional mortality. Studies have shown that matrix metalloproteinase-9 (MMP-9) levels are decreased postoperatively which may limits matrix degradation and participate in the development of peritoneal adhesions. In this proof-of-principle study, we evaluated the effect of gene therapy with catalytically inactive mutant MMP-9 on postoperative peritoneal adhesions in rats. METHODS Adenovirus encoding mutant MMP-9 (Ad-mMMP-9) or saline was instilled in the peritoneal cavity after cecal and parietal peritoneal injury in rats. Expression of mutant MMP-9 transcript was verified by sequencing. Adenovirus E4 gene expression, adhesion scores, MMP-9, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) expression were evaluated at sacrifice one week after treatment. RESULTS Both mutant MMP-9 transcripts and adenovirus E4 gene were expressed in Ad-mMMP-9 treated adhesions. Adhesions severity decreased significantly (p = 0.036) in the Ad-mMMP-9-treated compared with saline-treated adhesions. Expression of MMP-9 mRNA and protein were elevated (p = 0.001 and p = 0.029, respectively) in the Ad-mMMP-9-treated adhesions compared with saline-treated adhesions. While tPA levels were increased (p = 0.02) in Ad-mMMP-9 treated adhesions compared with saline-treated adhesions, TGF-β1 and PAI-1 levels were decreased (p = 0.017 and p = 0.042, respectively). No difference in mortality were found between groups (p = 0.64). CONCLUSIONS Mutant MMP-9 gene therapy effectively transduced peritoneal adhesions resulting in reduction of severity of primary peritoneal adhesions.
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Affiliation(s)
- Hussein Atta
- Department of Surgery, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt.
| | - Mahmoud El-Rehany
- Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt.
| | - Elke Roeb
- Department of Gastroenterology, Justus-Liebig University Giessen, Germany.
| | - Hend Abdel-Ghany
- Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt.
| | - Maggie Ramzy
- Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt.
| | - Shereen Gaber
- Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt.
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Oxidative stress and oocyte quality: ethiopathogenic mechanisms of minimal/mild endometriosis-related infertility. Cell Tissue Res 2015; 364:1-7. [DOI: 10.1007/s00441-015-2339-9] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 11/23/2015] [Indexed: 11/29/2022]
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24
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Fletcher NM, Awonuga AO, Neubauer BR, Abusamaan MS, Saed MG, Diamond MP, Saed GM. Shifting anaerobic to aerobic metabolism stimulates apoptosis through modulation of redox balance: potential intervention in the pathogenesis of postoperative adhesions. Fertil Steril 2015. [DOI: 10.1016/j.fertnstert.2015.06.041] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Abstract
INTRODUCTION Endometriosis affects 10% of women of reproductive age. It is defined as the presence of implanted active endometrial tissue outside the uterine cavity. The exact pathophysiology of endometriosis is still uncertain, although several optional etiological theories have been suggested. Being so common, a novel treatment for endometriosis is widely quested. Recent studies addressing the pathological characteristics of endometriosis have revealed a vicious cycle in which oxidative stress (OS) is generated, which in turn facilitates the implantation of the ectopic endometrium. At the same time, the generation of high amounts of reactive oxygen species further triggers a state of OS. AREAS COVERED The author examined the evidence associating OS and endometriosis. After establishing an association, a search for antioxidant agents that were investigated specifically on endometriosis patients are described including Vitamins C and E, melatonin, resveratrol, xanthohumol and epigallocatechin-3-gallate. A significant effect of all the reviewed antioxidants on endometriosis is reported. EXPERT OPINION Aiming for the reduction of OS as the treatment goal for endometriosis looks promising. However, since most of the studies are either in vitro or are animal based, further studies on human subjects are deemed necessary to elucidate the impact of OS reduction on patients with endometriosis.
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Affiliation(s)
- Avi Harlev
- a 1 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland , OH, USA.,b 2 Ben-Gurion University of the Negev, Faculty of Health Sciences, Soroka University Medical Center, Fertility and IVF Unit, Department of Obstetrics & Gynecology , Israel
| | - Sajal Gupta
- a 1 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland , OH, USA
| | - Ashok Agarwal
- c 3 American Center for Reproductive Medicine, Cleveland Clinic , Mail Code: X-11, 10681 Carnegie Avenue, Cleveland, OH 44195, USA +1 216 444 9485 ; +1 216 445 6049;
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Agacayak E, Tunc SY, Icen MS, Alabalik U, Findik FM, Yuksel H, Gul T. Honokiol Decreases Intra-Abdominal Adhesion Formation in a Rat Model. Gynecol Obstet Invest 2015; 79:160-7. [DOI: 10.1159/000367661] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 08/14/2014] [Indexed: 11/19/2022]
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Abstract
Intraperitoneal adhesions are frequently encountered and present significant challenges to the practicing surgeon, including increased operating time, bowel obstruction, pelvic pain, and infertility. Until recently, however, our knowledge of the biology of adhesion formation within the peritoneal cavity has been limited, which in turn limits prevention and treatment strategies for surgical patients. Extensive research has now led to an increased understanding of adhesion formation, with hypoxia playing a central role. Hypoxia stimulates a cascade that leads to oxidative stress, anaerobic metabolism, formation of free radicals, and ultimately the adhesion phenotype. By understanding the precipitants to adhesion development, we may begin to develop prevention and treatment therapies that will provide clinically significant improvement over the currently available approaches to limit postoperative adhesions.
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Affiliation(s)
- Kelli M Braun
- Department of Obstetrics and Gynecology, Georgia Regents University, 1120 15th St, BA-7300, Augusta, Georgia 30912
| | - Michael P Diamond
- Department of Obstetrics and Gynecology, Georgia Regents University, 1120 15th St, BA-7300, Augusta, Georgia 30912.
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28
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Juhasz-Böss I, Laschke MW, Müller F, Rosenbaum P, Baum S, Solomayer EF, Ulrich U. Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work. Geburtshilfe Frauenheilkd 2014; 74:733-742. [PMID: 25221341 DOI: 10.1055/s-0034-1382884] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Revised: 06/29/2014] [Accepted: 06/30/2014] [Indexed: 01/21/2023] Open
Abstract
Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosis and a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options.
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Affiliation(s)
- I Juhasz-Böss
- Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar
| | - M W Laschke
- Institut für Klinisch-Experimentelle Chirurgie, Universität des Saarlandes, Homburg
| | - F Müller
- Klinik für Gynäkologie und Geburtshilfe, Martin-Luther-Krankenhaus, Berlin
| | - P Rosenbaum
- Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar
| | - S Baum
- Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar
| | - E F Solomayer
- Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar
| | - U Ulrich
- Klinik für Gynäkologie und Geburtshilfe, Martin-Luther-Krankenhaus, Berlin
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Pirdel L, Pirdel M. Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis. Reproduction 2014; 147:R199-207. [PMID: 24599836 DOI: 10.1530/rep-13-0552] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
This article presents an overview of the involvement of iron overload-induced nitric oxide (NO) overproduction in apoptosis of peritoneal macrophages of women with endometriosis. We have postulated that the peritoneal iron overload originated from retrograde menstruation or bleeding lesions in the ectopic endometrium, which may contribute to the development of endometriosis by a wide range of mechanisms, including oxidative damage and chronic inflammation. Excessive NO production may also be associated with impaired clearance of endometrial cells by macrophages, which promotes cell growth in the peritoneal cavity. Therefore, further research of the mechanisms and consequences of macrophage apoptosis in endometriosis helps discover novel therapeutic strategies that are designed to prevent progression of endometriosis.
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Affiliation(s)
- Leila Pirdel
- Department of ImmunologyFaculty of Medicine, Islamic Azad University, Ardabil Branch, Ardabil 5615731567, IranDepartment of MidwiferyIslamic Azad University, Astara Branch, Astara, Iran
| | - Manijeh Pirdel
- Department of ImmunologyFaculty of Medicine, Islamic Azad University, Ardabil Branch, Ardabil 5615731567, IranDepartment of MidwiferyIslamic Azad University, Astara Branch, Astara, Iran
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Fletcher NM, Saed MG, Abuanzeh S, Abu-Soud HM, Al-Hendy A, Diamond MP, Saed GM. Nicotinamide adenine dinucleotide phosphate oxidase is differentially regulated in normal myometrium versus leiomyoma. Reprod Sci 2014; 21:1145-52. [PMID: 24520084 DOI: 10.1177/1933719114522552] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Uterine fibroids are the most common benign tumor in women. The goal of this study was to investigate whether nicotinamide adenine dinucleotide phosphate oxidase (NOX), a major source of superoxide and subsequent oxidative stress, was differentially regulated in myometrium versus leiomyoma. Expression levels of NOXs1-5, dual oxidase (DUOX), DUOX2, NOX organizer (NOXO) 1, NOX activator 1, p47(phox), p67(phox), and p22(phox) were determined in cells treated with hypoxia by real-time reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry in tissues. Expression of NOX4 increased in fibroid compared to myometrial tissues and cells. The NOX2, DUOX1, and p67(phox) were higher while p22(phox) was lower in fibroid than that in myometrial cells. Hypoxia increased NOX4, DUOX1, and NOXO1 and decreased p22(phox) in myometrial and reduced DUOX1 in fibroid cells. The NOX1, NOX3, NOX5, and DUOX2 were undetectable. Fibroid cells are characterized by a unique NOX profile, which promotes a severe prooxidant state that may be responsible for their development. Targeting these subunits may be beneficial for future therapeutic interventions.
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Affiliation(s)
- Nicole M Fletcher
- Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
| | - Mohammed G Saed
- Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
| | - Suleiman Abuanzeh
- Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
| | - Husam M Abu-Soud
- Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
| | - Ayman Al-Hendy
- Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN, USA
| | - Michael P Diamond
- Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, GA, USA
| | - Ghassan M Saed
- Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
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Liao CJ, Li PT, Lee YC, Li SH, Chu ST. Lipocalin 2 induces the epithelial–mesenchymal transition in stressed endometrial epithelial cells: possible correlation with endometriosis development in a mouse model. Reproduction 2014; 147:179-87. [DOI: 10.1530/rep-13-0236] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Lipocalin 2 (LCN2) is an induced stressor that promotes the epithelial–mesenchymal transition (EMT). We previously demonstrated that the development of endometriosis in mice correlates with the secretion of LCN2 in the uterus. Here, we sought to clarify the relationship between LCN2 and EMT in endometrial epithelial cells and to determine whether LCN2 plays a role in endometriosis. Antibodies that functionally inhibit LCN2 slowed the growth of ectopic endometrial tissue in a mouse model of endometriosis, suggesting that LCN2 promotes the formation of endometriotic lesions. Using nutrient deprivation as a stressor, LCN2 expression was induced in cultured primary endometrial epithelial cells. As LCN2 levels increased, the cells transitioned from a round to a spindle-like morphology and dispersed. Immunochemical analyses revealed decreased levels of cytokeratin and increased levels of fibronectin in these endometrial cells, adhesive changes that correlate with induction of cell migration and invasion.Lcn2knockdown also indicated that LCN2 promotes EMT and migration of endometrial epithelial cells. Our results suggest that stressful cellular microenvironments cause uterine tissues to secrete LCN2 and that this results in EMT of endometrial epithelial cells, which may correlate with the development of ectopic endometriosis. These findings shed light on the role of LCN2 in the pathology of endometrial disorders.
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Al-Jefout M, Tokushige N, Hey-Cunningham AJ, Manconi F, Ng C, Schulke L, Berbic M, Markham R, Fraser IS. Microanatomy and function of the eutopic endometrium in women with endometriosis. ACTA ACUST UNITED AC 2014. [DOI: 10.1586/17474108.4.1.61] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Biberoglu EH, Biberoglu KO. Prevention of Endometriosis. ENDOMETRIOSIS 2014:277-310. [DOI: 10.1007/978-4-431-54421-0_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Uterine fibroids are characterized by an impaired antioxidant cellular system: potential role of hypoxia in the pathophysiology of uterine fibroids. J Assist Reprod Genet 2013; 30:969-74. [PMID: 23812845 DOI: 10.1007/s10815-013-0029-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 05/31/2013] [Indexed: 01/25/2023] Open
Abstract
PURPOSE Fibroids are the most common smooth muscle overgrowth in women. This study determined the expression and the effect of hypoxia on two potent antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) on human fibroid cells. METHODS Immortalized human leiomyoma (fibroid) and myometrial cells were subjected to hypoxia (2 % O2, 24 h). Total RNA and cell homogenate were obtained from control and treated cells; CAT and SOD mRNA and activity levels were determined by real-time RT-PCR and ELISA, respectively. RESULTS Fibroid cells have significantly lower antioxidant enzymes, SOD and CAT mRNA and activity levels than normal myometrial cells (p < 0.05). Hypoxia treatment significantly increased SOD activity in myometrial cells while significantly decreasing CAT activity in fibroid cells (p < 0.05). There was no significant difference in CAT mRNA levels or activity in response to hypoxia in myometrial cells. Also, there was no significant difference in SOD mRNA levels in response to hypoxia in myometrial cells. CONCLUSION This is the first report to show that uterine fibroids are characterized by an impaired antioxidant cellular enzymatic system. More importantly, our results indicate a role for hypoxia in the modulation of the balance of those enzymes in fibroid and myometrial cells. Collectively, these results shed light on the pathophysiology of fibroids thereby providing potential targets for novel fibroid treatment.
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Bragatto FB, Barbosa CP, Christofolini DM, Peluso C, dos Santos AA, Mafra FA, Cavalcanti V, Hix S, Bianco B. There is no relationship between Paraoxonase serum level activity in women with endometriosis and the stage of the disease: an observational study. Reprod Health 2013; 10:32. [PMID: 23799909 PMCID: PMC3706249 DOI: 10.1186/1742-4755-10-32] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Accepted: 06/11/2013] [Indexed: 12/25/2022] Open
Abstract
Background Endometriosis is a chronic condition whose pathophysiology is unknown, but there is evidence suggesting a link with oxidative stress. Paraoxonase is a serum enzyme which circulates associated with high-density lipoprotein (HDL). It acts protecting HDL and LDL of lipid peroxidation. We aimed to compare the serum levels of PON-1 activity in women with endometriosis in different stages of the disease (minimal/mild and moderate/severe). Methods 80 infertile women with endometriosis diagnosed by laparoscopy/laparotomy with histologic confirmation of the disease were divided according to the American Society for Reproductive Medicine classification in minimal/mild (n = 33) and moderate/severe (n = 47) cases. Paraoxonase activity and arilesterase activity were measured by spectrophotometry. Body mass index and fasting glucose levels were also determined. Results The paraoxonase activity were 191.29 ± 22.41 U/l in women with minimal/mild endometriosis and 224.85 ± 21.50 U/l in women with moderate/severe disease (P = 0.274). Considering arilesterase level, the results showed 89.82 ± 4.61 U/l in women with minimal/mild endometriosis and 90.78 ± 3.43 U/l in moderate/severe disease (P = 0.888). Conclusions Evidence of lower paraoxonase activity in women with endometriosis was not found in this study. Besides, no difference was found considering minimal/mild or moderate/severe endometriosis.
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Affiliation(s)
- Felipe Barca Bragatto
- Division of Biochemistry, Department of Morphology, Faculdade de Medicina do ABC, Santo André, Santo André/SP, Brazil
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Kocadal NÇ, Attar R, Yıldırım G, Fıçıcıoğlu C, Özkan F, Yılmaz B, Yesildaglar N. Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. J Turk Ger Gynecol Assoc 2013; 14:81-6. [PMID: 24592080 PMCID: PMC3881748 DOI: 10.5152/jtgga.2013.53179] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Accepted: 04/24/2013] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE We aimed to determine the effects of melatonin treatment on endometrial implants in an oopherectomized rat endometriosis model. MATERIAL AND METHODS This study is a prospective, randomised, controlled experimental study. It was carried out at the Experimental Research Center of Yeditepe University (YUDETAM). Twenty-two, female, non-pregnant, nulligravid Spraque-Dawley albino rats were included in our study. Endometriosis was surgically induced in oopherectomized rats. Rats were randomised into two groups: control group and melatonin group. In the melatonin group, rats were treated with melatonin (20 mg/kg/day) for two weeks. After the operations were performed to assess the regression of the endometriotic lesions, melatonin treatment was stopped. At the end of the sixth week necropsies were performed to assess the rate of recurrence. The volume and histopathological scores of endometriotic foci were examined. RESULTS Volumes of the endometriotic lesions significantly decreased in the melatonin group. Also, when the melatonin group was analysed within itself, endometriotic lesion volumes decreased and histopathological scores increased significantly. CONCLUSION Melatonin causes regression of the endometriotic lesions in rats and improvement in their histopathological scores.
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Affiliation(s)
| | - Rukset Attar
- Department of Obstetrics and Gynecology, Yeditepe University School of Medicine, İstanbul, Turkey
| | - Gazi Yıldırım
- Department of Obstetrics and Gynecology, Yeditepe University School of Medicine, İstanbul, Turkey
| | - Cem Fıçıcıoğlu
- Department of Obstetrics and Gynecology, Yeditepe University School of Medicine, İstanbul, Turkey
| | - Ferda Özkan
- Department of Pathology, Yeditepe University School of Medicine, İstanbul, Turkey
| | - Bayram Yılmaz
- Department of Physiology and Experimental Studies and Research Center, Yeditepe University School of Medicine, İstanbul, Turkey
| | - Narter Yesildaglar
- Department of Obstetrics and Gynecology, Yeditepe University School of Medicine, İstanbul, Turkey
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Mıcılı SC, Göker A, Sayın O, Akokay P, Ergür BU. Lipoic acid decreases peritoneal adhesion formation in a rat uterine scar model. J Turk Ger Gynecol Assoc 2013; 14:76-80. [PMID: 24592079 DOI: 10.5152/jtgga.2013.22129] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Accepted: 04/08/2013] [Indexed: 02/01/2023] Open
Abstract
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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Affiliation(s)
- Serap Cilaker Mıcılı
- Department of Histology and Embryology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey
| | - Aslı Göker
- Department of Obstetrics and Gynecology, Celal Bayar University Faculty of Medicine, Manisa, Turkey
| | - Oya Sayın
- Department of Biochemistry, Dokuz Eylül University Learning Resources Center, İzmir, Turkey
| | - Pınar Akokay
- Department of Histology and Embryology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey
| | - Bekir Uğur Ergür
- Department of Histology and Embryology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey
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Park KS, Lee KE, Ku DH, Kim SJ, Park WS, Kim HY, Kwon MR, Youn YK. Antiadhesive effect and safety of oxidized regenerated cellulose after thyroidectomy: a prospective, randomized controlled study. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2013; 84:321-9. [PMID: 23741689 PMCID: PMC3671000 DOI: 10.4174/jkss.2013.84.6.321] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Revised: 03/05/2013] [Accepted: 03/20/2013] [Indexed: 11/30/2022]
Abstract
PURPOSE To evaluate the antiadhesive effects and safety of an oxidized regenerated cellulose (Interceed) after thyroidectomy. METHODS Seventy-six thyroidectomized patients were prospectively randomized into two groups with regard to the use of Interceed. We evaluated each group for their adhesive symptoms using four subjective and four objective items at the 2nd week, 3rd and 6th month after thyroidectomy. All patients were examined for vocal cord motility by indirect laryngoscope at each period. RESULTS Total adhesion scores at each postoperative follow-up period decreased with time, but were not significantly different in each group. The median score for swallowing discomfort for liquid was significantly lower in the Interceed group than in the control group 2 weeks after surgery. In addition, the severity of skin adhesion to the trachea was reduced in the Interceed group compared with the control group 6 months after surgery. During the study, there were no adverse effects or significant differences in postoperative complications between the groups. CONCLUSION Interceed appeared to be safe and effective in improving neck discomfort at early postoperative periods and preventing skin adhesion to the trachea 6 months after thyroidectomy.
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Affiliation(s)
- Kyoung Sik Park
- Department of Surgery, Konkuk University School of Medicine, Seoul, Korea
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Coccolini F, Ansaloni L, Manfredi R, Campanati L, Poiasina E, Bertoli P, Capponi MG, Sartelli M, Di Saverio S, Cucchi M, Lazzareschi D, Pisano M, Catena F. Peritoneal adhesion index (PAI): proposal of a score for the "ignored iceberg" of medicine and surgery. World J Emerg Surg 2013; 8:6. [PMID: 23369320 PMCID: PMC3573980 DOI: 10.1186/1749-7922-8-6] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Accepted: 01/29/2013] [Indexed: 12/24/2022] Open
Abstract
Peritoneal adhesions describe a condition in which pathological bonds form between the omentum, the small and large bowels, the abdominal wall, and other intra-abdominal organs. Different classification systems have been proposed, but they do not resolve the underlying problem of ambiguity in the quantification and definition of adhesions. We therefore propose a standardized classification system of adhesions to universalize their definition based on the macroscopic appearance of adhesions and their diffusion to different regions of the abdomen. By scoring with these criteria, the peritoneal adhesion index (PAI) can range from 0 to 30, unambiguously specifying precise adhesion scenarios. The standardized classification and quantification of adhesions would enable different studies to more meaningfully integrate their results, thereby facilitating a more comprehensive approach to the treatment and management of this pathology.
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Affiliation(s)
- Federico Coccolini
- General and Emergency Surgery department, Papa Giovanni XXIII hospital, Piazza OMS-Organizzazione Mondiale della Sanità 1, 24128, Bergamo, Italy.
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Dayton MT, Dempsey DT, Larson GM, Posner AR. New paradigms in the treatment of small bowel obstruction. Curr Probl Surg 2012; 49:642-717. [PMID: 23057861 DOI: 10.1067/j.cpsurg.2012.06.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Merril T Dayton
- Department of Surgery, SUNY Buffalo, Kaleida Health System, Buffalo, NY, USA
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Comhaire FH, Decleer W. Beneficial effect of food supplementation with the nutriceutical Improve® for the treatment of infertile couple. ASIAN PACIFIC JOURNAL OF REPRODUCTION 2012. [DOI: 10.1016/s2305-0500(13)60072-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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Bozkurt S, Arikan DC, Kurutas EB, Sayar H, Okumus M, Coskun A, Bakan V. Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation. J Pediatr Surg 2012; 47:1735-41. [PMID: 22974615 DOI: 10.1016/j.jpedsurg.2012.03.053] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Revised: 03/15/2012] [Accepted: 03/19/2012] [Indexed: 11/30/2022]
Abstract
BACKGROUND/PURPOSE The aim of the study was to evaluate the effects of selenium (Se) on ischemia/reperfusion (I/R) injury in rat ovaries. METHODS Thirty-five female Sprague-Dawley rats were randomly divided into 5 groups (n = 7): sham (S), I/R1, I/R2, Se1, and Se2. In the I/R1 and Se1 groups, 4 hours of ischemia was followed by 6 hours of reperfusion, and in the I/R2 and Se2 groups, 4 hours of ischemia was followed by 12 hours of reperfusion. In the Se groups, 30 minutes before reperfusion, a single dose of 0.2 mg/kg Se was administered intraperitoneally. The ovarian tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured biochemically. Tissue damage to ovarian tissue was scored by histopathologic examination. RESULTS The I/R groups had significantly higher MDA levels and lower CAT, SOD, and GPx activities than the sham group (P < .05). Although NO levels were significantly higher in the I/R1 group than in the sham group (P < .05), the NO levels in the I/R2 and sham groups were similar. Selenium pretreatment significantly lowered tissue MDA and NO levels and increased tissue SOD and GPx activities in the Se groups, compared with those in the I/R groups (P < .05). Catalase activities were significantly higher in the Se2 group than in the I/R2 group (P < .05). Catalase activities were higher in the Se1 group than in the I/R1 group, but the difference was not statistically significant. Treatment with Se significantly decreased the ovarian tissue damage scores in the Se2 group compared with those in the I/R2 group (P < .05). CONCLUSION Selenium is effective in preventing tissue damage induced by I/R in rat ovaries.
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Affiliation(s)
- Selim Bozkurt
- Kahramanmaras Sutcuimam University, Medical Faculty, Department of Emergency Medicine, Kahramanmaras, Turkey.
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Vichi S, Medda E, Ingelido AM, Ferro A, Resta S, Porpora MG, Abballe A, Nisticò L, De Felip E, Gemma S, Testai E. Glutathione transferase polymorphisms and risk of endometriosis associated with polychlorinated biphenyls exposure in Italian women: a gene–environment interaction. Fertil Steril 2012; 97:1143-51.e1-3. [DOI: 10.1016/j.fertnstert.2012.02.027] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Revised: 02/21/2012] [Accepted: 02/21/2012] [Indexed: 12/26/2022]
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Augoulea A, Alexandrou A, Creatsa M, Vrachnis N, Lambrinoudaki I. Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress. Arch Gynecol Obstet 2012; 286:99-103. [PMID: 22546953 DOI: 10.1007/s00404-012-2357-8] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2012] [Accepted: 04/19/2012] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. MATERIALS AND METHODS The etiology of this multifactorial disease is still unresolved and an increasing number of studies suggest that genetic, hormonal, environmental, immunological and oxidative factors may all play an important role in the pathogenesis of this disorder. CONCLUSIONS In this literature review, inflammatory activity, oxidative stress as well as genetic abnormalities and mutations have been studied in an effort to identify factors predisposing to endometriosis.
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Affiliation(s)
- A Augoulea
- 2nd Department of Obstetrics and Gynecology, University of Athens, Athens, Greece.
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Atta HM. Prevention of peritoneal adhesions: a promising role for gene therapy. World J Gastroenterol 2011; 17:5049-58. [PMID: 22171139 PMCID: PMC3235588 DOI: 10.3748/wjg.v17.i46.5049] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2011] [Revised: 07/14/2011] [Accepted: 07/21/2011] [Indexed: 02/06/2023] Open
Abstract
Adhesions are the most frequent complication of abdominopelvic surgery, yet the extent of the problem, and its serious consequences, has not been adequately recognized. Adhesions evolved as a life-saving mechanism to limit the spread of intraperitoneal inflammatory conditions. Three different pathophysiological mechanisms can independently trigger adhesion formation. Mesothelial cell injury and loss during operations, tissue hypoxia and inflammation each promotes adhesion formation separately, and potentiate the effect of each other. Studies have repeatedly demonstrated that interruption of a single pathway does not completely prevent adhesion formation. This review summarizes the pathogenesis of adhesion formation and the results of single gene therapy interventions. It explores the promising role of combinatorial gene therapy and vector modifications for the prevention of adhesion formation in order to stimulate new ideas and encourage rapid advancements in this field.
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46
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Landy SH, Kaniecki RG, Taylor FR. Abstracts and Citations. Headache 2011. [DOI: 10.1111/j.1526-4610.2011.02018.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Yildiz H, Durmus AS, Simsek H, Yaman I. The comparison of methylene blue and vitamin E in prevention of abdominal postoperative adhesion formation in rat uterine horn models: Biochemical and histopathologic evaluation. Acta Cir Bras 2011; 26:51-7. [PMID: 21271204 DOI: 10.1590/s0102-86502011000100010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2010] [Accepted: 10/20/2010] [Indexed: 01/08/2023] Open
Abstract
PURPOSE To compare the effects of vitamin E and 1% methylen blue solutions on prevention of experimentally induced adhesions in rats. METHODS Thirty seven female Spraque Dawley rats were randomized into four groups. First group was kept as sham operated group. An adhesion model was constituted on the left uterine horn of the other groups. The lesion areas of rats from the second, the third and the fourth groups were coated with 2 ml 0.9 % saline solution (C group), 10 mg vitamin E (VE group) and 1% methylen blue solutions (MB group), respectively. RESULTS Histopathologically, adhesion scores, mononuclear cell infiltration, oedema and fibrosis were more prominent in the MB group compared with C and VE groups. There were no significant differences between the groups in tissue glutathione peroxidase (GPx), catalase (CAT) activities and glutation (GSH) level, these parameters were slightly increased in group with VE supplementation though. The administration of VE and MB significantly decreased NO (P<0.01) levels when compared to the C group. The level of malondialdehyde (MDA) in the VE group was significantly lower (P<0.05) than those of the Sh and C groups. CONCLUSION Intraperitoneal methylen blue solutions treatments were more effective according to vitamin E in preventing the formation of intra-abdominal adhesion in a rat uterine horn model.
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Affiliation(s)
- Hamit Yildiz
- Department of Obstetrics and Gynecology, Firat University, Elazig, Turkey.
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Increased asymmetric dimethylarginine and enhanced inflammation are associated with impaired vascular reactivity in women with endometriosis. Atherosclerosis 2011; 219:784-8. [PMID: 21880316 DOI: 10.1016/j.atherosclerosis.2011.08.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Revised: 08/02/2011] [Accepted: 08/02/2011] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Enhanced inflammatory responses which may inhibit vascular reactivity, are associated with endometriosis development. Asymmetric dimethylarginine (ADMA), an inhibitor of endogenous nitric oxide synthase, is also implicated in endothelial dysfunction. We aimed to determine whether plasma ADMA and systemic inflammation are associated with endothelial function in women with endometriosis. METHODS We evaluated 41 women with and 28 women without endometriosis. Plasma levels of lipids and inflammatory markers such as high sensitive-C reactive protein (hs-CRP), serum amyloid protein A (SAA), and interleukin-6 (IL-6) were measured in the two groups. We also measured levels of ADMA and symmetric dimethylarginine (SDMA). High-resolution ultrasonography measured flow-mediated vasodilation (FMD) to assess vasodilatory responses. RESULTS FMD was significantly lower in women with endometriosis compared to those without endometriosis (8.39 ± 0.43% vs 10.79 ± 0.54%, P = 0.001). While plasma lipid levels did not differ significantly between groups, levels of AMDA, but not SDMA, were significantly higher in women with endometriosis (409.7 ± 10.1 pmol/L vs 383.0 ± 48.3 pmol/L, P = 0.04). Inflammatory markers were also significantly higher in these women (hs-CRP: 1053.3 ± 252.0 ng/mL vs 272.0 ± 83.3 ng/mL, P = 0.02; SAA: 8.00 ± 1.53 μg/mL vs 3.82 ± 0.42 μg/mL, P = 0.04; IL-6: 2.73 ± 0.75 pg/mL vs 1.05 ± 0.60 pg/mL, P = 0.04). FMD was negatively correlated with plasma levels of ADMA (r = -0.37, P=0.01) and log hs-CRP (r = -0.34, P = 0.01). CONCLUSION Increased plasma ADMA levels and enhanced inflammation are associated with inhibited endothelial function in women with endometriosis.
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Karp BI, Sinaii N, Nieman LK, Silberstein SD, Stratton P. Migraine in women with chronic pelvic pain with and without endometriosis. Fertil Steril 2011; 95:895-9. [PMID: 21145540 PMCID: PMC3415219 DOI: 10.1016/j.fertnstert.2010.11.037] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2010] [Revised: 10/15/2010] [Accepted: 11/11/2010] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis. DESIGN Prospective study of headache, pelvic pain, and quality of life before laparoscopic surgery for pelvic pain. Endometriosis was diagnosed pathologically. Headaches were classified as migraine or non-migraine using International Headache Society criteria. SETTING Clinical research hospital. PATIENT(S) 108 women in a clinical trial for chronic pelvic pain (NCT00001848). INTERVENTION(S) Laparoscopy to diagnose endometriosis, assessment by neurologist to assess headaches. MAIN OUTCOME MEASURE(S) Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis. Headache frequency, severity and relationship to pelvic pain and endometriosis. RESULT(S) Lifetime prevalence of definite or possible migraine was 67% of women with chronic pelvic pain. An additional 8% met criteria for possible migraine. Migraine was no more likely in women with endometriosis than those without. Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone. CONCLUSION(S) Migraine headache is common in women with chronic pelvic pain, regardless of endometriosis, and contributes to disability in those with both conditions. The strong association suggests a common pathophysiology.
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Affiliation(s)
- Barbara Illowsky Karp
- National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
| | - Ninet Sinaii
- Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | - Lynnette K. Nieman
- Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | | | - Pamela Stratton
- Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
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Surgery-induced changes in red blood cell and plasma lipid peroxidation, enzymatic and non-enzymatic antioxidants, and blood hematology of female rats: protective role of methylene blue and vitamin E. Eur J Obstet Gynecol Reprod Biol 2011; 155:89-93. [DOI: 10.1016/j.ejogrb.2010.11.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2010] [Revised: 08/18/2010] [Accepted: 11/02/2010] [Indexed: 11/20/2022]
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