Is montelukast effective in regression of endometrial implants in an experimentally induced endometriosis model in rats?

Tapisiz, Omer/0000-0002-7128-8086WOS: 000348826200002PubMed: 25462212Objective: Montelukast, a selective antagonist of Type 1 cysteinyl leukotriene receptors (CysLT(1)Rs), antagonizes the proinflammatory and proasthmatic activities of CysLT(1)Rs. We investigated the effect of montelukast on a surgically induced endometriosis rat model. Study design: Thirty-two sexually mature, cycling, female Wistar-Albino rats, in which endometriotic implants were surgically induced, were randomly divided into three groups. Group I [Montelukast (M), 10 rats)] was given 1.6 mg/kg/day of oral montelukast sodium. Group II [Leuprolide acetate (L), 11 rats] was given 1 mg/kg single dose of s.c.leuprolide acetate. Group III [Control (C), 11 rats] received saline solution through an orogastric tube and served as controls. After a 3-weeks medication, the rats were sacrificed to investigate the endometriotic implants for size and morphological and histological characteristics, including immunoreactivity of MMP-2 and VEGF. Results: The mean area of implants decreased from 48.2 +/- 24.7 to 293 +/- 15.8 mm(2) in Group I (M) (P = 0.008) and from 62 +/- 32.1 to 39.9 +/- 18.1 mm(2) in Group II(L) (P = 0.003). In Group III (C), the mean area increased from 41.1 +/- 31.1 to 60.4 +/- 37.1 mm(2) (P = 0.025). Histopathological analysis showed statistically significant lower scores in rats treated with montelukast compared to leuprolide and controls. MMP H scores were not different between the groups in both epithelial and stromal MMP-2 immunostaining. VEGF H scores were statistically lower in Group I (M) in epithelial VEGF immunostaining when compared to Group II(L) and Group III (C) (P = 0.006). Conclusion(s): Montelukast may effectively cause a significant decrease in the area of endometriotic implants. (C) 2014 Elsevier Ireland Ltd. All rights reserved

Effect of the non-specific matrix metalloproteinase inhibitor Doxycycline on endometriotic implants in an experimental rat model.

The aim of this study was to investigate the possible therapeutic effects of Doxycycline (Dox) on endometriotic lesions in an experimental rat model. Thirty-seven female Wistar albino rats with surgically induced endometriosis were randomized and divided into four groups. The rats were administered 5 mg/kg/day oral Dox in Group 1 (low-dose Dox group, n=9), 20 mg/kg/day oral Dox in Group 2 (high-dose Dox group, n=10) and 1 mg/kg single dose, subcutaneous leuprolide acetate in Group 3 (leuprolide acetate group, n=9). The rats in Group 4 (control group, n=9) were given no medication. The rats received medication for three weeks and were then sacrificed to evaluate the morphological and histological features of the implants. Matrix metalloproteinase (MMP)-9 immunoreactivity of the implants was also evaluated. The size of the endometriotic implants decreased in Groups 1-3 but statistically significant differences were not observed among the groups. The mean surface area of the endometriotic implants decreased from 69.3±30.8 to 52.1±27.0 mm² in Group 1 (P>0.05), from 60.2±18.9 to 38.6±28.7 mm² in Group 2 (P>0.05) and from 58.1±33.1 to 26±9.0 mm² in Group 3 (P=0.03). The epithelial MMP-9 immunohistochemical score was significantly higher in Group 1 and lower in Group 3 when compared with the control group (Group 4) (P=0.042 and P=0.014, respectively). When the stromal MMP-9 immunohistochemical and histopathological scores of the endometriotic implants were compared, no statistically significant differences were found among the groups. Although there was no statistically significant difference, Dox reduced the endometriotic implant area in the rat endometriosis model. Further studies are required to investigate the potential efficacy of Dox in endometriosis due to its widespread use and tolerability

Effects of melatonin on uterine hypertrophy/hyperplasia: A preliminary experimental rat study

Endometrial hyperplasia is a process of endometrial proliferation that results in a thickening of the endometrial tissue. Melatonin might be able to change the pathophysiological process and prognosis into a positive way that might prevent and heal endometrial hyperplasia, which is the first stage of endometrial cancer. For this perspective, we tried to investigate the effect of melatonin on uterine hypertrophy/hyperplasia in an experimental rat model. Forty Wistar-Albino rats were undergone bilateral oophorectomy and randomized into four groups. To create a model of uterine hypertrophy/hyperplasia in all groups, except the control group [C] (n = 10), 4 mg/kg/day estradiol hemihydrate were given for 14 days. The uterine hypertrophy/hyperplasia was evaluated histopathologically in the left uterine horns, then the groups were treated for 14 days as follows; melatonin (10 mg/kg/day/po) [M] (n = 10), melatonin + estradiol hemihydrate (10 mg/kg/day/po and 4 mg/kg/day/po) [M + E] (n = 10), and dark environment [D] (n = 10). Finally, the effects of the melatonin were examined histopathologically in the right uterine horns. An uterine hypertrophy/hyperplasia model was established in all groups compared to the control group (p < 0.05). In the [M] and [M + E] groups, epithelial cell height and luminal epithelial cell height significantly decreased (41?m vs 12?m, p = 0.005; 14?m vs 10?m, p = 0.005, respectively for [M] group) and (32?m vs 14?m, p = 0.012; 17?m vs 10?m, p = 0.017, respectively for [M + E] group). The [D] group exhibited a significant decrease in epithelial cell height (33?m vs 20?m, p = 0.017). With or without estrogen exposure, melatonin-treated and physiologically melatonin-released rats experienced a significant uterine hypertrophy/hyperplasia recovery. Melatonin may have protective effects on endometrial hyperplasia

Effect of the non-specific matrix metalloproteinase inhibitor Doxycycline on endometriotic implants in an experimental rat model

The aim of this study was to investigate the possible therapeutic effects of Doxycycline (Dox) on endometriotic lesions in an experimental rat model. Thirty-seven female Wistar albino rats with surgically induced endometriosis were randomized and divided into four groups. The rats were administered 5 mg/kg/day oral Dox in Group 1 (low-dose Dox group, n=9), 20 mg/kg/day oral Dox in Group 2 (high-dose Dox group, n=10) and 1 mg/kg single dose, subcutaneous leuprolide acetate in Group 3 (leuprolide acetate group, n=9). The rats in Group 4 (control group, n=9) were given no medication. The rats received medication for three weeks and were then sacrificed to evaluate the morphological and histological features of the implants. Matrix metalloproteinase (MMP)-9 immunoreactivity of the implants was also evaluated. The size of the endometriotic implants decreased in Groups 1-3 but statistically significant differences were not observed among the groups. The mean surface area of the endometriotic implants decreased from 69.3 +/- 30.8 to 52.1 +/- 27.0 mm(2) in Group 1 (P>0.05), from 60.2 +/- 18.9 to 38.6 +/- 28.7 mm(2) in Group 2 (P>0.05) and from 58.1 +/- 33.1 to 26 +/- 9.0 mm(2) in Group 3 (P=0.03). The epithelial MMP-9 immunohistochemical score was significantly higher in Group 1 and lower in Group 3 when compared with the control group (Group 4) (P=0.042 and P=0.014, respectively). When the stromal MMP-9 immunohistochemical and histopathological scores of the endometriotic implants were compared, no statistically significant differences were found among the groups. Although there was no statistically significant difference, Dox reduced the endometriotic implant area in the rat endometriosis model. Further studies are required to investigate the potential efficacy of Dox in endometriosis due to its widespread use and tolerability