Regression Of Endometriotic Implants Research Articles

Vitamin C is effective for the prevention and regression of endometriotic implants in an experimentally induced rat model of endometriosis

ObjectiveEndometriosis is a chronic inflammatory disease pathologically defined as the presence of endometrial-like tissue outside the uterine cavity. It is one of the most important diseases affecting women of reproductive age. The process of endometriotic implant growth is mediated by many complex interactions of immunologic, hormonal, genetic, and environmental mediators. Vitamin C (ascorbic acid), besides playing a role in preventing invasion and metastasis, is an antioxidant having anti-inflammatory and -angiogenic effects. In this study, we aimed to investigate the effect of vitamin C on the prevention and regression of endometriotic implants in a rat model of endometriosis. Materials and MethodsThis was a prospective, comparative, experimental animal study. After endometriotic implants were induced simultaneously, rats were divided into three groups. Group A was given 500 mg/kg of intravenous vitamin C every 2 days, starting immediately after implantation (n = 11). All rats had a second operation 21 days after the initial one and had the lesion volumes measured. Group B was given 500 mg/kg of intravenous vitamin C every 2 days, starting 21 days after this operation (n = 11). All rats were sacrificed 21 days after the third operation. Implant volume, weight measurements, and histopathological evaluation of the lesions were carried out. Group A received vitamin C throughout the study, while Group C (n = 11) was not given any medication. The findings in the three groups were compared. ResultsAt the second laparotomy after the induction, Group A had the smallest implant volume with a statistically significant difference compared to Group B (p = 0.012). The end-of-study volumes of endometriotic implants of group B were significantly smaller than the first volumes (p < 0.05). ConclusionIntravenous vitamin C treatment might have a suppressive effect on the prevention of endometriotic implant induction and regression of endometriotic implant volumes.

Melatonin causes regression of endometriotic implants in rats by modulating angiogenesis, tissue levels of antioxidants and matrix metalloproteinases.

The aim of this study was to test if melatonin causes regression of endometriotic implants and whether it influences implant levels of superoxide dismutase (SOD), malondialdehyde (MDA), vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in rats. Endometriotic implants were introduced surgically to 20 female Wistar albino rats, which were either treated with melatonin via intraperitoneal injection for four weeks (melatonin group, n = 10) or with saline (control group, n = 10) after a second-look laparotomies. The main outcome measures included volume (mm(3)) and weight (mg) of explants and tissue levels of SOD, MDA, VEGF, TIMP-2 and MMP-9. Before and after treatment implant volumes of the melatonin group were decreased significantly (P < 0.01) while there was no significant difference between the pretreatment and posttreatment implant volumes of the control group. Moreover, weight (P < 0.05) and histologic score (P < 0.05) of implants of the melatonin-treated rats were significantly lower than controls. Activity of SOD and TIMP-2 staining in melatonin group was significantly higher (both P < 0.01) while there were significant reductions in implant levels of VEGF and MMP-9 in melatonin group (both P < 0.01) than controls. Melatonin induces the regression of endometriotic implants in rats by modulating implant levels of SOD, MDA, VEGF, MMP-9 and TIMP-2.

Regression of endometrial implants treated with vitamin D3 in a rat model of endometriosis

Endometriosis is one of the most frequent gynecological diseases. In addition to their side effects, available medical therapies may decrease fertility. Current understanding of endometriosis focuses on the role of the immune system in its pathophysiology. Recent research shed light on the immunomodulatory effect of vitamin D3. Thus, this study was designed to study the effect of vitamin D3 on regression of endometriotic implants in a rat surgical model. Vitamin D3 reduced cyst cross sectional area by 48.8%. Histologically, vitamin D treatment produced fibrosis as well as apoptosis in the stroma. The results of the present study suggest that vitamin D3 administration may have a beneficial effect in treating endometriosis.

Sunitinib as an anti-endometriotic agent

Endometriosis is one of the most frequent diseases in gynecology. Currently available medical therapies for this disease are unsatisfactory. Based on current understanding of the pathogenic mechanisms in endometriosis especially the similarity between this disease and cancer, this study was designed to investigate the efficacy of the anticancer drug sunitinib in treating endometriosis. The effect of sunitinib on regression of endometriotic implants was studied in a rat surgical model. Sunitinib reduced cyst cross sectional area by 78.8% and caused complete cyst disappearance in 50% of the animals. Histologically, extensive fibrosis was detected in sunitinib-treated group with positive reaction in TUNEL assay indicating that apoptosis is a mechanism of action.

Immunological regulation of Chinese herb Guizhi Fuling Capsule on rat endometriosis model

To investigate the immunological regulation of Guizhi Fuling Capsule (GZFLC) on rat endometriosis. Twenty-seven rats, in which endometriotic implants were induced by transplanting autologous uterine tissue to the peritoneum, were randomly divided into three groups equally: (1) the GZFLC group of low dose (480 mg/kg/day); (2) the GZFLC group of high dose (1,920 mg/kg/day); and (3) the model group(saline solution). Another 10 rats were treated as sham operation group. After rats were treated for four weeks, we examined the alterations of implants volume, the percentage of CD4(+) T lympholeukocyte, the activity of NK cell and the expression of cytokines (MCP-1 and ICAM-1) on each group. Statistical analysis showed that posttreatment volumes were significantly reduced compared with pretreatment in GZFLC groups, whereas there was no significant change in the model group. The percentage of CD4(+) T lympholeukocyte and the activity of NK cell in GZFLC groups significantly increased to the level of the sham group compared with the model. RT-PCR and immunohistochemistry showed that the endometria of the sham operation and treatment groups were similar on expression level of MCP-1 and ICAM-1. GZFLC plays an important role in the regression of endometriotic implants by immunological regulation in the rat model.

Comparison of aromatase inhibitor (letrozole) and immunomodulators (infliximab and etanercept) on the regression of endometriotic implants in a rat model

Objective Novel treatment strategies are needed in the treatment of endometriosis due to limited success rates with the currently available options. As inflammatory and immunological mechanisms have been shown to be involved in the mechanism of the disease, new modalities are likely to emerge. We investigated the effects of infliximab (INF), etanercept (ETA) and letrozole on the regression of experimental endometriosis. Study design In this experimental randomized trial, endometriosis was induced surgically in 44 adult female Sprague–Dawley rats. Establishment of implants was confirmed in 41 animals by a second operation on the 21st day. The rats were then randomly divided into four groups. Group I ( n = 10) served as controls. Group II ( n = 11) received letrozole (0.18 mg/kg, i.p.), group III ( n = 10, i.p.) ETA (2.016 mg/kg, i.p.), and group IV ( n = 10) INF (15.12 mg/kg, i.p.) for a second 21-day period. Endometriotic implant size along with peritoneal fluid VEGF level and immunoreactivity were determined before and after the treatment in each group. Results Endometriotic implant size reduced in all treatment groups. The effect of letrozole and ETA on implant size was similar but was significantly better than INF. Level of VEGF in peritoneal fluid did not change in any treatment group but post-treatment VEGF immunoreactivity was found significantly lower in the letrozole treated group. Conclusions Letrozole and ETA caused a regression on the implant size in experimental endometriosis. The only group with decreased VEGF expression was letrozole.

Etanercept causes regression of endometriotic implants in a rat model

To determine the effects of etanercept (anti-TNF-α) on surgically induced endometriosis in a rat model. This is a prospective, randomized, controlled, experimental study that was carried out at the Experimental Research Center of Yeditepe University (YUDETAM). Thirty female nonpregnant, nulligravid Wistar-Hannover albino rats were used. The summary of the technique: surgical induction of endometriosis, administration of estrogen for 2 weeks, and laparotomy; administration of etanercept for 2 weeks following the induction of endometriosis and laparotomy; administration of estrogen for 2 weeks and necropsy. The volume and histopathological scores of the endometriotic foci were evaluated. One-hundred twenty uterine horns were implanted in 30 rats. Endometriosis was completely formatted in 112 lesions (93.3%). No rats were lost. In the etanercept group, the lesions' volumes were 83.9 ± 13.1, 47.2 ± 8.4, and 96.7 ± 34.8 mm(3) at the end of the second week (pretreatment stage), at the end of the fourth week (post-treatment stage), and at the end of the sixth week, respectively (P = 0.007). Histopathologic scores were 2.3 ± 0.2, 1.7 ± 0.2, and 1.9 ± 0.1, respectively (P = 0.08). The changes in the other groups were not statistically significant. Etanercept, a fusion protein consisting of human recombinant soluble TNF receptor-2, neutralizes TNF activity. Anti-TNF therapy could be a new non-hormonal therapeutic option for the treatment of endometriosis in humans.

Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9

We sought to test if metformin could regress endometriotic explants in rats. After inducing endometriotic implants and randomization of female Wistar albino rats, they were given 25 and 50 mg/kg/day of oral metformin in group A (n = 9) and B (n = 8), respectively, for 28 days. Group C (n = 9) was given saline as placebo. Mean volume, weight, and histologic score of implants in groups A (P < .01, P < .05, and P < .05, respectively) and B (P < .01, P < .05, and P < .05, respectively) were significantly lower than in group C. The activity of superoxide dismutase and tissue inhibitor of metalloproteinase-2 staining in groups A (P < .05 and P < .01, respectively) and B (P < .01 and P < .01, respectively) was significantly higher than in the control group. Moreover, there were more significant reductions in implant levels of vascular endothelial growth factor and matrix metalloproteinase-9 in groups A (both P < .001) and B (both P < .001) than in group C. Metformin causes regression of endometriotic implants in rats.

Comparison of immunimodulators (infliximab and etanercept) and aramotase inhibitor (letrazol) on the regression of endometriotic implants in the rat model

OBJECTIVE: To evaluate the effect of infliximab (INF), etanercept (ETA) and letrazol on the regression of an experimentally induced endometriosis in a rat model. DESIGN: Prospective, randomized animal study. MATERIALS AND METHODS: Forty-one adult female Spraque Dawley rats in which endometriotic implants were induced by transplanting autologous uterine tissue to ectopic sites on the peritoneum. After obtaining the endometriotic implants, the 41 rats were randomly divided into four groups: Group 1 (INF [15.12 mg/kg], 10 rats), group 2 (ETA [2.016 mg/kg], 10 rats), Group 3 (letrozole [0.18 mg/kg], 11 rats), group 4 (control [no medication], 10 rats). After 21 days, all rats were euthanized to assess the implants' size, vascular endothelial growth factor (VEGF) level in peritoneal fluid and VEGF immunoreactivity. RESULTS: There is a statistically meaningful difference between the control group and letrozole group as far as the VEGF and implant results are concerned (p<0,001 and p=0.024 respectively). The implant results of the letrozole group were lower than those of the INF group (p=0.036) and still lower than those of the ETA group in terms of VEGF results (p=0.006).TableComparison of pre, post VEGF and implant results among groups.VEGF Pre (pg/ml)VEGF Post (pg/ml)Implantation Pre (mm2)Implantation Post (mm2)Infliximab(n:10)178.5(169-188)179(169-206)16(9-49)4(0-16)Etanercept (n:10)182(169-212)184(176-206)16(0-49)0(0-4)Letrozol (n:11)181(162-317)174(160-183)9(4-16)1(0-4)Control (n:10)192(174-206)195(178-211)16(0-25)9(0-16)p value∗Results are given as median (min-max), ∗Kruskal-Wallis test0.135〈0.0010.1130.002∗ Results are given as median (min-max), ∗Kruskal-Wallis test Open table in a new tab However, statistically no significant differences between pre and post VEGF immunoreactivity have been found in all groups CONCLUSIONS: INF, ETA and letrozole have regressed endometriotic implants, but letrozole has been statistically and meaningfully high compared to other groups

Fenofibrate causes regression of endometriotic implants: a rat model

Fenofibrate -a peroxisome proliferator-activated receptor-a agonist- is an angiostatic agent that is commonly used in human liver diseases, therefore it may interfere with the angiogenetic process required for endometriosis. In a rat endometriosis model, we demonstrated that peritoneal implant areas and vascular endothelial growth factor levels in the peritoneal flud were significantly decreased in high dose or low dose finofibrate and luprolide acetate treated groups compared to control.

Doxycycline causes regression of endometriotic implants: a rat model

Doxycycline (Dox) has a number of non-antibiotic properties. One of them is the inhibition of matrix metalloproteinase (MMP) activity. The aim of this study was to assess the effects of Dox in a rat endometriosis model. Endometriosis was surgically induced in 40 rats by transplanting of endometrial tissue. After 3 weeks, repeat laparotomies were performed to check the implants and the animals were randomized into four groups: Group I, low-dose Dox (5 mg/kg/day); Group II, high-dose Dox (40 mg/kg/day); Group III, leuprolide acetate 1 mg/kg single dose, s.c.; and Group VI (controls), no medication. The treatment, initiated on the day of surgery and continuing for 3 weeks, was administered to the study groups. Three weeks later, the rats were euthanized and the implants were evaluated morphologically and histologically for immunoreactivity of MMP-2 and -9, and interleukin-6 (IL-6) concentration in the peritoneal fluid was assayed. Treatment with leuprolide acetate, or high-dose or low-dose Dox caused significant decreases in the implant areas compared with the controls (P = 0.03, P = 0.006, and P = 0.001, respectively). IL-6 levels in peritoneal fluid decreased in Group I (P = 0.02) and Group III (P < 0.05). MMP H scores were significantly lower in the group that received low-dose Dox in both epithelial and stromal MMP-2 and -9 immunostaining when compared with the control group [P = 0.048, P = 0.002, P = 0.007 and P = 0.002, respectively, MMP-2 (epithelia), MMP-2 (stroma), MMP-9 (epithelia) and MMP-9 (stroma)]. Low-dose Dox caused regression of endometriosis in this experimental rat model.