THE AMELIORATIVE EFFECTS OF LUPEOL AND FLUTAMIDE ON DEHYDROEPIANDROSTERONE-INDUCED UTERINE HYPERFIBROSIS IN MICE

Rezaei Golmisheh, A and Sadrkhanlo, R.A and Malekinejad, H and Ahmadi, A (2017) THE AMELIORATIVE EFFECTS OF LUPEOL AND FLUTAMIDE ON DEHYDROEPIANDROSTERONE-INDUCED UTERINE HYPERFIBROSIS IN MICE. The Journal of Urmia University of Medical Sciences, 26 (10). pp. 923-934.

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Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive ages that may contribute to uterine complications such as endometrial hyperplasia and hyperfibrosis. Hyperandrogenemia is the key factor in the pathophysiology of PCOS. Based on recent finding concerning anti-androgen effects of Lupeol, we aimed to study the effects of this triterpenoid on uterine damages of hyperandrogenemia and compare them with Flutamide. Materials & Methods: Forty prepubertal female albino mice aged 25 days were randomly assigned to experimental groups. Control group (n=10) received 0.1 ml/day sesame oil (IP) for 35 consecutive days. The rest of animals received 60 mg/kg B.W./day DHEA dissolved in 0.1 ml sesame oil for twenty days and afterward for fifteen days each group (n=10) was treated either sesame oil[group PCOS(P)], Lupeol 40 mg/kg B.W. (group L) or Flutamide 10 mg/kg B.W. (group F). Weight gains were recorded weekly. At the end of treatment animals were humanly euthanized under deep ether anesthesia and uterine samples were collected. Histological sections were prepared and stained with H&E, AZAN and Toluidine blue methods for histomorphometric, fibrosis and mast cells count analyses. Fibrosis quantification was performed based on image analysis using Matlab software (V. 8.1.0). Results: At the end of treatment period, group P demonstrated remarkable increase of body weight whereas Lupeol and Flutamide treatment decreased weight gain significantly (P<0.05). Endometrium thickness (μm), average percentage of collagen fibers in uterine tissue (%) and average number of mast cells in histological sections (n) in group P (331.6 ± 63.8, 14.6 ± 1.65, 3.02 ± 0.89, respectively) increased significantly compared to group C (235.3 ± 28.1, 8.10 ± 1.41, 1.47 ± 0.55) and decreased in L (199.8 ± 51.3, 4.07 ± 0.90, 1.02 ± 0.69) and F (194.6 ± 41.4, 5.21 ± 0.39, 1.31 ± 0.60) groups significantly compared to group P (P<0.05). Conclusion: We conclude that Lupeol is able to reduce uterine hyperfibrosis and endometrial hyperplasia induced by DHEA in mice and these are similar to effects of Flutamide. These effects of Lupeol could be in part because of its anti- androgen receptor effects

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