{"paper_id":"428ea5a5-4d0d-422a-a0c0-24f8762faa5f","body_text":"Annals of Agricultural and Environmental Medicine 2018, Vol 25, No 4, 587–592\nwww.aaem.plORIGINAL  ARTICLE\nDisrupted iron metabolism  in peritoneal fluid \nmay induce oxidative stress in the peritoneal \ncavity of women with endometriosis\nGrzegorz Polak1, Bartłomiej Barczyński1, Iwona Wertel1, Wojciech Kwaśniewski1, \nWiesława Bednarek1, Magdalena Derewianka-Polak2, Karolina Frąszczak1, Marcin Olajossy2, \nJan Kotarski1\n1 Department of Oncological Gynecology and Gynecology, Medical University of Lublin  \n2 Department of Psychiatry and Psychiatry Rehabilitation, Medical University of Lublin\nPolak G, Barczyński B, Wertel I, Kwaśniewski W, Bednarek W, Derewianka-Polak M, Frąszczak K, Olajossy M, Kotarski J. Disrupted iron \nmetabolism in peritoneal fluid may induce oxidative stress in the peritoneal cavity of women with endometriosis. Ann Agric Environ Med. \n2018; 25(4): 587–592. https://doi.org/10.26444/aaem/75802\nAbstract\nIntroduction and objective.  Data on the possible role of peritoneal fluid free radical-mediated oxidative damage in the \npathogenesis of endometriosis still remains inconsistent. The aim of the study was to determine iron metabolism markers \nand their influence on oxidative stress parameters in the peritoneal fluid of women with endometriosis.  \nMaterials and method.  110 women with endometriosis and 119 patients with benign ovarian cysts were included in the \nstudy. All visible peritoneal fluid was aspirated during laparoscopy from the anterior and posterior cul-de-sacs. under direct \nvision to avoid blood contamination. Haemoglobin, iron, total oxidative status, and total antioxidant status were measured \nusing standard colourimetric kits.  \nResults. Haemoglobin, iron levels, as well as total oxidative status values were significantly higher, whereas total antioxidant \nstatus values were significantly lower in the peritoneal fluid of patients with endometriosis, in comparison to the reference \ngroups. No differences were observed in peritoneal fluid concentrations of all parameters measured in relation to the phase \nof the menstrual cycle.  \nConclusions. Peritoneal fluid of women with endometriosis is characterized by disrupted iron metabolism. This is most \nlikely related to an increased number of erythrocytes in the peritoneal cavity of endometriotic women, which leads to a \nhigher concentration of haemoglobin in this environment. Impaired iron homeostasis may have a significant influence on \nthe pathophysiology of peritoneal endometriosis by the direct impact of haemoglobin derivatives and/or formation of \nthe pro-inflammatory and pro-oxidative environment. Peritoneal cavity oxidative stress occurs predominantly in women \nin advanced stages of the disease.\nKey words\nEndometriosis, peritoneal fluid, oxidative stress, haemaglobin, iron, total oxidative status, total antioxidant status\nINTRODUCTION\nFree radicals have been implicated in the  pathogenesis \nof numerous diseases, including endometriosis. In \nendometriotic patients pro-oxidant-antioxidant balance may \nbe disturbed by different cells found in the peritoneal cavity \n(erythrocytes. apoptotic endometrial cells. macrophages), as \nwell as some environmental factors like dioxins and heavy \nmetal ions.\nFoyouzi et  al. [1] proved that different reactive oxygen \nspecies may modulate the growth of endometrial tissue. \nPro-oxidant-antioxidant imbalance may contribute to the \ndevelopment of excessive growth of endometrial stromal cells \nin endometriosis. However, literature data on the possible \nrole of peritoneal fluid (PF) free radical-mediated oxidative \ndamage in the pathogenesis of endometriosis still remain \ninconsistent.\nIn 1987, Zeller et  al. [2] showed that in women with \nendometriosis chronic stimulation of the peritoneal cavity \nresident macrophages by ectopic endometrial implants \nprovokes constitutive release of large quantities of reactive \noxygen products, e.g. superoxide anion, hydrogen peroxide, \nand singlet oxygen. However, some later studies did not \nconfirm these findings as being clinically significant, showing \nno differences in the concentration of reactive oxygen forms \nin both native PF and PF supernatants in endometriotic and \nhealthy women. Free oxygen radicals concentration was \nnot associated with age, menstrual cycle phase, PF volume, \nor clinical stage [3, 4]. Free radicals may show asymmetric \ndistribution in the peritoneal cavity, i.e. increased radicals \nconcentration was detected only locally, close to endometrial \nimplants, but not in the entire peritoneal cavity [5].\nIt has been proved in animal studies. that the intraperitoneal \ncombined instillation of superoxide dismutase (SOD) and \ncatalase significantly reduced the formation of intraperitoneal \nadhesions at endometriosis sites [6]. Ota et al. [7] found an \nincreased manganese SOD, copper/zinc SOD, and glutathione \nperoxidase in the eutopic endometrium of patients with \nendometriosis, but not in healthy individuals. Furthermore, \na significantly lower concentration and activity of SOD was \ndemonstrated in PF of women with endometriosis [8, 9], \nalthough previous investigations by the authors of the current \nstudy [10] and the results of Ishikawa et al. [11] did not confirm \nthis observation. It has also been proved that glutathione \nAddress for correspondence: Grzegorz Polak, Department of Oncological \nGynecology and Gynecology, Medical University of Lublin\nE-mail: polakg@yahoo.com\nReceived: 18 June 2016; accepted: 3 April 2017; first published June 2017\n\nAnnals of Agricultural and Environmental Medicine 2018, Vol 25, No 4\nGrzegorz Polak, Bartłomiej Barczyński, Iwona Wertel, Wojciech Kwaśniewski, Wiesława Bednarek, Magdalena Derewianka-Polak  et al. Disrupted iron metabolism …\nperoxidase PF activity is lower in women with endometriosis \n[9]. In a prospective pilot study of infertile women submitted \nfor assisted reproduction procedures, Petean et al. showed \na significant decrease in vitamin E serum levels in a group \nof patients with endometriosis [12]. Completely opposite \nresults were presented by Jackson et al. [13]. Observations of \nPF vitamin E concentration are also inconsistent [14, 15, 16]. \nSzczepańska et al. [9] demonstrated lower total antioxidant \nstatus in PF of infertile women with endometriosis. However, \nno such difference between endometriotic and healthy \nindividuals was confirmed in a study by Ho et al. [17] and a \nprevious trial by the authors of this study [18].\nOBJECTIVES\nThe results of trials presented by different authors on the \nrole of oxidative stress phenomenon in endometriosis \netiopathogenesis are incoherent, and the conclusions are \noften contradictory. Thus, the design of the research was \nto carry out complex investigations on the role of oxidative \nstress process in endometriosis. The objective of the study \nwas to determine iron metabolism markers and their \ninfluence on oxidative stress parameters in PF of women \nwith endometriosis.\nMATERIALS AND METHOD\n229 women aged 15–53 who underwent diagnostic or \ntherapeutic laparoscopy were examined. Clinically and \nhistologically confirmed diagnosis established the following \ngroups: women with endometriosis (E. n=110), and as the \nreference groups, patients with simple serous (R1, n=78) \nand dermoid (R2, n=41) ovarian cysts. In each case. \nendometriosis was staged according to the American Society \nfor Reproductive Medicine classification [19]. The disease was \nfound to be minimal (E1) in 23 cases, mild (E2) in 25 patients, \nmoderate (E3) in 39 women, and severe (E4) in 23 cases.\nMedical history of the patients and basic clinical \nexamination showed no general chronic diseases, except \nfor the condition which was the indication for laparoscopy. \nMean age of women did not differ significantly between the \nstudied groups. Similarly, no significant difference was found \nin the phase of menstrual cycle of the time of laparoscopic \nprocedures between women in all study groups.\nAll patients signed an informed consent and approval for \nthe study was obtained from the Lublin Medical University \nEthics Committee.\nAll visible PF was aspirated during laparoscopy from \nthe anterior and posterior cul-de-sacs under direct vision \nto avoid blood contamination. Samples were immediately \ncentrifuged, supernatants were aspirated and stored at -70 \nC until analysis. Haemoglobin concentration in the PF \nwas measured in duplicate using a commercially available \nenzyme-linked immunoassay kit (Imundiagnostik AG. \nCat. No. K7816). PF iron levels were determined using the \ncolorimetric kit (Stanbio Iron and Total Binding Capacity \n(TIBC) – Stanbio Laboratory. Cat. No. 370). Estimation \nof Total Oxidative Status (TOS) and Total Antioxidant \nStatus (TAS) was performed using commercially available \ncolorimetric kits (PerOx-Immundiagnostic AG. Cat. No. \nKC5100; ImAnOx- Immundiagnostic AG. Cat. No. KC5200).\nAll data were tested with the Shapiro-Wilk test for \nnormality. Statistical significance was determined with the \nMann-Whitney U and H Kruskal-Wallis tests. P value less \nthan 0.05 was considered statistically significant. Data are \npresented as medians (Me), minima (Min), maxima (Max). \nlower and upper quartiles.\nRESULTS\nHaemoglobin PF concentrations.  Haemaglobin PF levels \nin patients with endometriosis were significantly higher, \ncompared to women from both reference groups (p<0.01). \nSignificantly higher PF haemaglobin concentration was \nobserved in patients with all stages of endometriosis, \ncompared to women from both reference groups. No \nsignificant difference in PF haemaglobin concentrations was \nfound between women with different endometriosis stages \n(Fig. 1; Tab. 1).\nPF haemaglobin concentration did not differ significantly \nbetween the subgroups of women in the follicular and the \nluteal phase of the menstrual cycle (Me. range; 102, 11.8–\n126.3 ng/ml vs. 106.4. 69–241.6 ng/ml; p=0.8).\nA significant positive correlation (p<0.001) between PF \nhaemaglobin concentrations and iron levels. and between \nhaemaglobin concentrations and PF TOS. A negative \n(p<0.001) correlation was found between PF haemaglobin \nlevels and TAS.\nTable 1. P values for comparisons of haemaglobin PF concentrations \nbetween study groups\nVariable:\nHaemaglobin\nP values for multiple comparisons (two-sided comparisons)\nKruskal-Wallis test\nR1 R2 E1 E2 E3 E4\nR1 1.000 0.008 <0.001 <0.001 <0.001\nR2 1.000 0.021 <0.001 <0.001 <0.001\nE1 0.008 0.021 1.000 1.000 0.486\nE2 <0.001 <0.001 1.000 1.000 1.000\nE3 <0.001 <0.001 1.000 1.000 1.000\nE4 <0.001 <0.001 0.486 1.000 1.000\nFigure 1. PF concentrations of haemaglobin in the study groups\n588\n\nAnnals of Agricultural and Environmental Medicine 2018, Vol 25, No 4\nGrzegorz Polak, Bartłomiej Barczyński, Iwona Wertel, Wojciech Kwaśniewski, Wiesława Bednarek, Magdalena Derewianka-Polak  et al. Disrupted iron metabolism …\nPF iron levels.  Levels of iron were significantly higher \n(p<0.01) in PF of women with endometriosis, compared to \npatients with serous and dermoid ovarian cysts. Significantly \nhigher PF concentration of iron was found in women with \nmild, moderate and severe endometriosis, compared to \npatients from both reference groups. Patients with minimal \nendometriosis had higher PF iron levels, compared to women \nwith serous ovarian cysts, but PF iron levels did not differ \nsignificantly between women with stage I of endometriosis \nand subjects with dermoid cysts. Patients with III and IV \nstages of the disease had significant higher iron levels, \ncompared to women with minimal endometriosis (Fig. 2; \nTab. 2).\nPF iron concentration did not differ significantly between \nthe subgroups of women in the follicular and the luteal phase \nof the menstrual cycle (Me. range; 138.4, 49.1–511.1 mg/l vs. \n179.8. 46.9–568.4 mg/l; p=0.8).\nA significant positive correlation (p<0.001) was found \nbetween PF iron concentrations and iron levels, and between \niron concentrations and PF TOS. Significant negative \n(p<0.001) correlation was found between PF haemaglobin \nlevels and TAS.\nPF Total Oxidative Status.  PF Total Oxidative Status was \nsignificantly higher in patients with endometriosis, compared \nto women with serous and dermoid ovarian cysts. TOS of \nPF of women with I, III and IV stages of endometriosis \nwere significantly higher, compared to patients from both \nreference groups (p<0.01). However, no significant differences \nwere found between PF TAS of women with women with \nmild endometriosis, and patients form the reference groups \n(Fig. 3; Tab. 3).\nPF TOS did not differ significantly between the subgroups \nof women in the follicular and the luteal phase of the \nmenstrual cycle (Me. range; 133.5, 3.7–667.4 µmol/l vs. 120.6, \n1.5–625.9 µmol/l; p=0.7).\nA significant positive correlation (p<0.001) was found \nbetween PF TOS and both iron and haemaglobin levels. \nSignificant negative (p<0.001) correlation was found between \nPF TOS and TAS.\nPF Total Antioxidant Status. PF Total Antioxidant Status was \nsignificantly (p<0.01) lower in women with endometriosis., \ncompared to patients with serous and dermoid ovarian cysts. \nBy analyzing PF TAS in women with different stages of the \ndisease, it was noted that they were lower only in the subgroup \nof patients with stage IV endometriosis, compared to women \nfrom both reference groups. Patients with mild endometriosis \nhad lower PF TAS, compared to women with serous ovarian \ncysts (Fig. 4; Tab. 4).\nPF TAS did not differ significantly between the subgroups \nof women in the follicular and the luteal phase of the \nmenstrual cycle (Me. range; 391, 41.-1505.3 µmol/l vs. 370.7, \n63–3818.1 µmol/l; p=0.6).\nA significant negative correlation (p<0.001) was found \nbetween PF TAS concentrations and TOS, iron, and \nhaemaglobin levels.\nTable 2. P values for comparisons of iron PF concentrations between \nstudy groups\nVariable:\nIron\nP values for multiple comparisons (two-sided comparisons)\nKruskal-Wallis test\nR1 R2 E1 E2 E3 E4\nR1 1.000 0.034 <0.001 <0.001 <0.001\nR2 1.000 0.516 <0.001 <0.001 <0.001\nE1 0.034 0.516 1.000 0.015 <0.001\nE2 <0.001 <0.001 1.000 1.000 0.095\nE3 <0.001 <0.001 0.015 1.000 1.000\nE4 <0.001 <0.001 <0.001 0.095 1.000\nFigure 2. PF concentrations of iron in the study groups\n589\nTable 3. P values for comparisons of PF TOS between study groups\nVariable:\nTOS\nP values for multiple comparisons (two-sided comparisons)\nKruskal-Wallis test\nR1 R2 E1 E2 E3 E4\nR1 1.000 0.021 0.054 0.007 <0.001\nR2 1.000 0.026 0.065 0.015 <0.001\nE1 0.021 0.026 1.000 1.000 1.000\nE2 0.054 0.065 1.000 1.000 0.386\nE3 0.007 0.015 1.000 1.000 0.241\nE4 <0.001 <0.001 1.000 0.386 0.241\nFigure 3. PF TOS in the study groups\n\nAnnals of Agricultural and Environmental Medicine 2018, Vol 25, No 4\nGrzegorz Polak, Bartłomiej Barczyński, Iwona Wertel, Wojciech Kwaśniewski, Wiesława Bednarek, Magdalena Derewianka-Polak  et al. Disrupted iron metabolism …\nDISCUSSION\nAccording to Sampson’s hypothesis [20], the most important \nprocess initiating the development of the disease is retrograde \nmenstruation into the peritoneal cavity. Because the \nphenomenon of ‘retrograde menstruation’ occurs in most \nof women at reproductive age, it is claimed that endometriosis \nresults from dysfunctions of mechanisms participating in \nthe elimination of endometrial cells in the peritoneal cavity, \nerythrocytes, and the products of their decomposition [21].\nThe presented study demonstrates that PF of women \nsuffering from endometriosis contains a higher concentration \nof haemaglobin, compared to PF of healthy individuals. The \nresults of this study clearly demonstrate a dysfunction of \nmechanisms responsible for the elimination of haemaglobin. \nThis observation generally refers to patients with minimal \nand mild endometriosis in whom bleeding from ectopic \nimplants cannot be intense because of the early stage of the \ndisease. The obtained results suggest that dysfunctions of \nerythrocytes or haemaglobin elimination from the peritoneal \ncavity may constitute the fundamental basis of endometriosis \npathophysiology.\nNo significant differences in PF haemaglobin concentration \nin women in various stages of endometriosis were \ndemonstrated. In patients with minimal and mild disease, \nwith low volume implants, the main source of erythrocytes \nin the peritoneal cavity is probably the process of ‘retrograde \nmenstruation’. However, in advanced stages of the disease, \noften accompanied by obstruction of oviducts, an essential \nsource of erythrocytes in the peritoneal cavity may be \nbleeding from endometrial implants. Lack of significant \ndifferences in PF haemaglobin concentration between women \nin different stages of the disease indirectly proves that the \nconcentration of erythrocytes in this environment is similar \nin all stages of endometriosis.\nThe degradation of haemaglobin leads to the release of its \nprotein component and heme. Heme’s catabolism is related \nto the formation of many biologically-active substances, \nincluding iron ions. In the presented study, a higher \nconcentration of iron was observed in PF of women suffering \nfrom endometriosis, compared to the reference groups. These \nresults are in accordance with those obtained by other authors \n[5, 22, 23, 24]. It was also noted that the concentration of iron \nin PF of women in advanced stages of endometriosis was \nhigher, compared to patients suffering from stage I of the \ndisease. These results are indirectly confirmed by the positive \ncorrelation between PF iron concentration. and the stage of \nendometriosis. demonstrated by Arumugam and Yip [23].\nAnother important observation is the positive correlation \nbetween the concentrations of haemaglobin and iron. This \nconfirms that the main source of iron in the peritoneal \ncavity is the haemoprotein. Similar to the results obtained \nby Van Langendonckt et al. [5], significant differences in PF \nconcentrations of both haemaglobin and iron were observed \nin relation to the phase of the menstrual cycle, which is a \nvery interesting finding. Theoretically, the concentrations \nof these substances should be increased after menstrual \nbleeding, i.e. in the follicular phase of the cycle. The results \nobtained in the presented study are consistent with those of \nHalme et al. [25] who demonstrated presence of erythrocytes \nin PF beyond the phase of menstrual bleeding. Similarly, PF \nhaemaglobin and iron concentrations observed in this study \nindicate the existence of other than ‘retrograde menstruation’ \nas the possible source of bleeding within the peritoneal cavity. \nIn women suffering from endometriosis, one of the causes \nmay be endometrial implants. Hypothetically, the presence \nof these substances in healthy patients in the luteal phase of \nmenstrual cycle may also be explained by ovulation.\nHigher PF haemaglobin concentrations in PF of women \nsuffering from endometriosis may have other negative \nimplications. Both free heme and iron ions accumulating in \nthe peritoneal cavity may damage its epithelium, increasing \nthe adhesion of endometrium cells [5, 23]. Heme, by \nstimulating the expression of cell adhesion molecules (ICAM-\n1, VCAM-1) and E-selectine in peritoneal and endometrial \ncells, facilitate the implantation of endometrial cells [26]. \nMoreover, it was proved that heme may simulate macrophages \nto produce a wide range of cytokines, including TNF-α. IL-1 \nand IL-6 involved in the pathogenesis of endometriosis [27]. \nIncreased expression of heme oxygenase leads to an increased \nproduction of biliverdin, iron ions and carbon monoxide – \na strong vasodilator, which may stimulate vascularization \nnecessary for the development of implants [5, 28]. It may also \nbe speculated that a higher concentration of haemaglobin in \nthe PF of women with endometriosis may cause a release of \nhigher amounts of the superoxide radical, and hence induce \noxidation stress in the peritoneal cavity.\nA very important and pioneer discovery which may \nconstitute a link between iron metabolism and the degree \nof free radical processes intensity in PF, is a positive \ncorrelation between the TOS values and the concentrations \nof haemaglobin and iron. These results prove a direct \nrelationship between an increased concentration of iron from \n590\nTable 4. P values for comparisons of PF TAS between study groups\nVariable\nTAS\nP values for multiple comparisons (two-sided comparisons)\nKruskal-Wallis test\nR1 R2 E1 E2 E3 E4\nR1 1.000 0.089 0.893 0.004 <0.001\nR2 1.000 0.344 1.000 0.051 0.007\nE1 0.089 0.344 1.000 1.000 1.000\nE2 0.893 1.000 1.000 1.000 0.979\nE3 0.004 0.051 1.000 1.000 1.000\nE4 <0.001 0.007 1.000 0.979 1.000\nFigure 4. PF TAS in the study groups\n\n\nAnnals of Agricultural and Environmental Medicine 2018, Vol 25, No 4\nGrzegorz Polak, Bartłomiej Barczyński, Iwona Wertel, Wojciech Kwaśniewski, Wiesława Bednarek, Magdalena Derewianka-Polak  et al. Disrupted iron metabolism …\nhaemaglobin and the intensity of oxidative processes in PF. \nResults obtained in the presented study clearly demonstrate \nthat the cause of the intensified activity of free radicals \nin women suffering from endometriosis is an increased \nconcentration of iron. The source of this element is most \nlikely the decomposed erythrocytes entering the peritoneal \ncavity during ‘retrograde menstruation’, or released during \nhaemorrhages from the ectopic endometrial implants. \nIn the current study, no differences were found between \nthe TOS of PF, regardless to the phase of the menstrual \ncycle. Similarly, no differences were found on examining \nhaemaglobin and iron concentrations in PF. In an indirect \nway, these results confirm the theory that the activity of free \nradicals in the peritoneal cavity, initiated by haemaglobin \nand iron, is constant throughout the whole menstrual \ncycle. This is an interesting observation concerning women \nwith endometriosis. While planning the study, the authors \nexpected that the intensity of these processes, as well as iron \nPF concentration, would be higher during the follicular \nphase of the cycle.\nThe total antioxidant status of the peritoneal fluid \nof endometriotic patients recruited for this study was \nsignificantly lower than in women from the both reference \ngroups. This result proves that the defence potential against \nfree radicals in the peritoneal cavity of such women is \nsignificantly lower. This seems to be a natural consequence \nof increased PF free radical processes. The significant negative \ncorrelation between TOS and TAS values demonstrated in \nthe current study confirms the hypothesis. This relationship \nalso demonstrates the strong reliability and validity of \nthe presented data. Increased oxidative processes lead to \nimpairment of the mechanisms of antioxidant defence. The \nresults presented also confirm the results of studies that \nshowed decreased levels of superoxide dismutase, as well \nas vitamins C and E, in PF of women with endometriosis \n[12, 15, 14, 29], and are consistent with the results obtained \nby Szczepanska et al. [9] who demonstrated a decrease of \nthe total antioxidant status of PF in endometriotic women. \nPrevious research by the authors of the presented study [18] \nand a study by Ho et al. [17], showed quite different results. \nHowever, they were based on relatively small cohorts of \nwomen, therefore, the results obtained in the present study \nseem to be more representative.\nAnalyzing the values of PF total antioxidant status of \nwomen with endometriosis in relation to the stage of the \ndisease, it was concluded that impairment of the antioxidant \nprocesses did not occur in women with minimal and mild \ndisease. It was demonstrated that only PF antioxidant \nstatus of women suffering from severe endometriosis was \nsignificantly lower, compared to both reference groups. \nHowever, in women suffering from stage III of the disease, \nTAS was significantly lower, compared to patients with serous \novarian cysts. This is an important finding for endometriosis \npathophysiology because these results suggest that the \nmechanisms of antioxidant defence are not impaired by \nthe presence of endometrial implants in early stages of the \ndisease. Thus, it can be speculated that the disturbances of the \nantioxidant defence occur in advanced disease as a result of \na progressive increase in the volume of ectopic endometrial \ntissue in the peritoneal cavity. The defence defects against \nfree radicals may result from the excessive activity of free \nradical processes, stimulated by the intensified metabolism \nof iron in the peritoneal cavity of women with endometriosis. \nThe impairment of antioxidant mechanisms of PF may not \nbe considered a cause of the disease. but rather a result of its \nprogressive development.\nTotal antioxidant status of the peritoneal fluid did not \ndiffer significantly between the phases of the menstrual cycle. \nAdditionally, as previously described, no differences in PF \nconcentration of free radical processes indicators between \nthe phases of the cycle were found. Taken together, these \nobservations suggest that the parameters of the pro- and \nanti-oxidant balance of PF are not related to sex hormones \nchanges during the menstrual cycle.\nCONCLUSIONS\nPF of women with endometriosis is characterized by \ndisrupted iron metabolism. This is most likely related to an \nincreased number of erythrocytes in the peritoneal cavity of \nendometriotic women, which leads to a higher concentration \nof haemaglobin in this environment. This phenomenon may \nresult from a primary defect of the mechanisms responsible \nfor eliminating erythrocytes and their decomposition \nproducts, as well as from an increased number of erythrocytes \npresent in the peritoneal cavity that exceeds the capacity of \nthese mechanisms. Impaired iron homeostasis may have a \nsignificant influence on the pathophysiology of endometriosis, \nby direct impact of haemaglobin derivatives and formation of \nthe proinflammatory and prooxidative environment in the \nperitoneal cavity. 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