Summary
To evaluate the potential effect of Ankaferd Blood Stopper (ABS) and oxytocin (OT) in an experimental endometriosis model, 18 female Sprague Dawley rats were used in this study. The animals were divided randomly into three groups after surgical induction of endometriosis: group 1: control group (isotonic NaCl, 1 mL/kg/day, intramuscular, n=6); group 2: OT group (OT, 80 U/kg/day, intramuscular, n=6); group 3: ABS group (ABS, 1.5 mL/kg/day, intraperitoneal, n=6). Each group was treated for four weeks (two times per week). Volumes of endometriotic explants were measured in biopsy samples for histopathological analysis. Vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor (TNF-α) levels were measured in plasma and peritoneal fluid. Endometriotic explant volumes were significantly decreased after OT administration (P<0.0001). The epithelial score was significantly decreased in both treatment groups compared to the control group (P<0.05). TUNEL immunohistochemistry showed more apoptotic changes in the endometriosis foci (gland epithelium and surrounding tissue) in the OT group than in the control group (P<0.05). The levels of VEGF, MCP-1, and TNF-α were significantly reduced in the OT group (P<0.05), whereas no significant changes in protein levels were found in the ABS-applied group. The results indicate that OT has greater potential as a therapeutic agent in experimentally induced peritoneal endometriosis, where ABS, which is a VEGF modulator, appears to act through different mechanisms to show its palliative effects on a rat model of peritoneal endometriosis.
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References
Bulun SE. Endometriosis. N Engl J Med, 2009,360(3): 268–279
Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol, 1927, 14:422–469
Braun DP, Ding J, Dmowski WP. Peritoneal fluid-mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis. Fertil Steril, 2002, 78(4):727–732
Jiang QY, Wu RJ. Growth mechanisms of endometriotic cells in implanted places: a review. Gynecol Endocrinol, 2012, 28(7):562–567
Bourlev V, Volkov N, Pavlovitch S, et al. The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions. Reproduction, 2006, 132(3):501–509
Ulukus M, Ulukus EC, Tavmergen Goker EN, et al. Expression of interleukin-8 and monocyte chemotactic protein 1 in women with endometriosis. Fertil Steril, 2009, 91(3):687–693
Mechsner S, Bartley J, Loddenkemper C, et al. Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. Fertil Steril, 2005, 83:1220–1231
Simsek Y, Celik O, Karaer A, et al. Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the treatment of experimental endometriosis. Arch Gynecol Obstet, 2012,286(3):777–783
Goker H, Haznedaroglu I, Ercetin S, et al. Haemostatic Actions of the Folkloric Medicinal Plant Extract Ankaferd Blood Stopper. J Int Med Res, 2008, 36(1):163–170
Lee SJ, Umano K, Shibamoto T, et al. Identification of volatile components in basil (Ocimum basilicum L.) and thyme leaves (Thymus vulgaris L.) and their antioxidant properties. Food Chem, 2005, 91(1):131–137
Simsek C, Selek S, Koca M, et al. Proteomic and transcriptomic analyses to explain the pleiotropic effects of Ankaferd blood stopper. SAGE Open Med, 2017, 5:2050312117722569
Sheela ML, Ramakrishna MK, Salimath BP. Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra. Int Immunopharmacol, 2006, 6(3):494–498
Vernon MW, Wilson EA. Studies on the surgical induction of endometriosis in the rat. Fertil Steril, 1985, 44(5):684–694
Güney M, Oral B, Karahan N, et al. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril, 2008, 89(4):934–42
Petersson M, Wiberg U, Lundeberg T, et al. Oxytocin decreases carrageenan induced inflammation in rats. Peptides, 2001, 22(9):1479–1484
Cipil HS, Kosar A, Kaya A, et al. In vivo hemostatic effect of the medicinal plant extract Ankaferd Blood Stopper in rats pretreated with warfarin. Clin Appl Thromb Hemost, 2009, 15(3):270–276
Keenan JA, Williams-Boyce PK, Massey PJ, et al. Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertil Steril, 1999, 72(1):135–141
Giudice LC, Kao LC. Endometriosis. Lancet, 2004,364(9447):1789–1799
Young VJ, Ahmad SF, Brown JK, et al. Peritoneal VEGF-A expression is regulated by TGF-β1 through an ID1 pathway in women with endometriosis. Sci Rep, 2015, 5:16859
Griffith JS, Rodgers AK, Schenken RS. Reviews: in vitro models to study the pathogenesis of endometriosis. Reprod Sci, 2010, 17(1):5–12
Jiang L, Yan Y, Liu Z, et al. Inflammation and endometriosis. Front Biosci (Landmark Ed.), 2016,21: 941–948
Wei J, Zhao B, Zhang C, et al. Jiawei Foshou San Induces Apoptosis in Ectopic Endometrium Based on Systems Pharmacology, Molecular Docking, and Experimental Evidence. Evid Based Complement Alternat Med, 2019, 2019:2360367
Dmowski WP, Ding J, Shen J, et al. Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis. Hum Reprod, 2001,16(9): 1802–1808
Celik O, Aydin S, Celik N, et al. Peptides: Basic determinants of reproductive functions. Peptides, 2015, 72:34–43
Yuan L, Liu S, Bai X, et al. Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice. J Neuroinflammation, 2016, 13(1):77
Haznedaroglu BZ, Beyazit Y, Walker SL, et al. Pleiotropic cellular, hemostatic, and biological actions of Ankaferd hemostat. Crit Rev Oncol Hematol, 2012, 83(1):21–34
Hasgul R, Uysal S, Haltas H, et al. Protective effects of Ankaferd blood stopper on aspirin-induced oxidative mucosal damage in a rat model of gastric injury. Toxicol Ind Health, 2014, 30(10):888–895
Büyük B, Beyazit F. The efficacy of Ankaferd Blood Stopper® in an experimental Asherman syndrome model created in rats. Turk J Obstet Gynecol, 2019, 16(1):7–14
Yeniel AÖ, Erbas O, Ergenoglu AM, et al. Effect of oxytocin treatment on explant size, plasma and peritoneal levels of MCP-1, VEGF, TNF-α and histopathological parameters in a rat endometriosis model. Eur J Obstet Gynecol Reprod Biol, 2014, 175:134–139
Salmassi A, Acar-Perk B, Schmutzler AG, et al. Apoptosis resistance in endometriosis. Bioimpacts, 2011, 1(2):129–134
Nie J, Liu X, Guo SW. Immunoreactivity of oxytocin receptor and transient receptor potential vanilloid type 1 and its correlation with dysmenorrhea in adenomyosis. Am J Obstet Gynecol, 2010, 202(4):346.e 1–8
Huang M, Li X, Guo P, et al. The abnormal expression of oxytocin receptors in the uterine junctional zone in women with endometriosis. Reprod Biol Endocrinol, 2017, 15(1):1
Guo SW, Mao X, Ma Q, et al. Dysmenorrhea and its severity are associated with increased uterine contractility and overexpresion of oxytocin receptor (OTR) in women with symptomatic adenomyosis. Fertil Steril, 2013, 99(1):231–240
Sippel LM, Allington CE, Pietrzak RH, et al. Oxytocin and Stress-related Disorders: Neurobiological Mechanisms and Treatment Opportunities. Chronic Stress (Thousand Oaks), 2017,1
Garrido-Urbani S, Deblon N, Poher AL, et al. Inhibitory role of oxytocin on TNF-α expression assessed in vitro and in vivo. Diabetes Metab, 2018,44(3):292–295
Ahmed MA, Elosaily GM. Role of Oxytocin in deceleration of early atherosclerotic inflammatory processes in adult male rats. Int J Clin Exp Med, 2011, 4(3):169–178
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This study was supported by Ege University School of Medicine-Research Funds, Izmir, Turkey (No. 2011-TIP-090).
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Hortu, I., Ozceltik, G., Karadadas, E. et al. The Role of Ankaferd Blood Stopper and Oxytocin as Potential Therapeutic Agents in Endometriosis: A Rat Model. CURR MED SCI 40, 556–562 (2020). https://doi.org/10.1007/s11596-020-2213-1
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DOI: https://doi.org/10.1007/s11596-020-2213-1