scholarly journals Naloxone Breeding Effectiveness in Rat Suffering from Nitric Oxide-induced Polycystic Ovary Syndrome

2015 ◽  
Vol 6 (2) ◽  
pp. 67-72
Author(s):  
Manizheh Karami ◽  
Fatemeh Lakzaei ◽  
MohammadReza Jalali Nadoushan

ABSTRACT Background and objective Polycystic ovary syndrome (PCOS) can be induced in Wistar rats by over production of nitric oxide (NO). This study evaluated the efficacy of naloxone on the breeding characteristics of rats suffering from nitric oxide induced PCOS. Materials and methods Twenty-four female Wistar rats(200–250 gm) were kept as virgin under standard conditions. They were divided into four groups (n = 6). One group of the animals received L-arginine (50 mg/kg) intraperitoneally (i.p.) for 9 days/once a day. Another group was administered naloxone hydrochloride (0.4 mg/kg, i.p.) prior to injection of L-arginine. The third group was injected solely naloxone. Control group received saline solution (1 ml/kg, i.p.). After the treatments, all female rats were coupled with the intact males. They were then separated by observation of vaginal plaques; it was considered as day 0 of pregnancy. Eventually, they were operated on days 18 to 19 of the gestation to collect the animals’ ovaries. The samples were studied for pathological evidence. The fetal number and weight along with the fetal crown-rump length (CRL) were measured. Results The ovaries obtained from the L-arginine treated group had large cysts with thickened granulosa cell layer in contrast to those of the control or naloxone treated rats (p < 0.0001). The number of fetus though showed a decrease in the L-arginine treated rats (3 ± 1), but the fetal weight or fetal CRL did not change (p > 0.05). Conclusion This study may clearly illustrate the polycystic characteristics in the L-arginine treated group. It may particularly display the breeding efficacy of naloxone in rats with PCOS. How to cite this article Karami M, Lakzaei F, Nadoushan MRJ. Naloxone Breeding Effectiveness in Rat Suffering from Nitric Oxide-induced Polycystic Ovary Syndrome. Int J Infertil Fetal Med 2015;6(2):67-72.

2018 ◽  
Vol 27 (6) ◽  
pp. 515-522 ◽  
Author(s):  
Atilla Karateke ◽  
Recep Dokuyucu ◽  
Hatice Dogan ◽  
Tumay Ozgur ◽  
Zeynel Abidin Tas ◽  
...  

Objective: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In the present study, we investigated the therapeutic effects of erdosteine in letrozole-induced PCOS in rats. Methods: Thirty-two Wistar albino female rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group (PCOS+MET), and PCOS-erdosteine group (PCOS+Erd). PCOS was induced by administering letrozole; such rats presented with sex hormone disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic follicles, and increasing fasting insulin levels. After induction of PCOS, metformin (500 mg/kg/day) and erdosteine (100 mg/kg/day) were given orally to the treatment groups for 30 days. Serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, circulating estrone (E1), estradiol (E2), testosterone, and androstenedione were evaluated. The ovaries were graded histologically. Results: Weights of ovarian tissues (p < 0.05) and the number of atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in the PCOS+Erd group; the corpus luteum number was significantly higher in the PCOS+Erd group (p < 0.01) as compared with the PCOS group. Lipid parameters (total-C, LDL-C, and TG), E1 (estrone), E1/E2 ratio, testosterone, and androstenedione significantly decreased, while HDL-C and E2 (estradiol) significantly increased in the PCOS+Erd group as compared with the PCOS group. Moreover glucose, insulin, and HOMA-IR were reduced with treatment of erdosteine (p > 0.05, p < 0.001, and p < 0.001, respectively). Conclusion: It is suggested that erdosteine may be used in the treatment of PCOS as an alternative to metformin. It appears that our findings might be supported by clinical and molecular studies.


Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 434-445 ◽  
Author(s):  
Manuel Maliqueo ◽  
Miao Sun ◽  
Julia Johansson ◽  
Anna Benrick ◽  
Fernand Labrie ◽  
...  

Studying the mechanisms for the complex pathogenesis of polycystic ovary syndrome (PCOS) requires animal models with endocrine, reproductive, and metabolic features of the syndrome. Hyperandrogenism seems to be a central factor in PCOS, leading to anovulation and insulin resistance. In female rats, continuous administration of letrozole, a nonsteroidal inhibitor of P450 aromatase, at 400 μg/d starting before puberty induces hyperandrogenemia and reproductive abnormalities similar to those in women with PCOS. However, despite high circulating testosterone levels, these rats do not develop metabolic abnormalities, perhaps because of their supraphysiological testosterone concentrations or because estrogen synthesis is completely blocked in insulin-sensitive tissues. To test the hypothesis that continuous administration of lower doses of letrozole starting before puberty would result in both metabolic and reproductive phenotypes of PCOS, we performed a 12-wk dose-response study. At 21 d of age, 46 female Wistar rats were divided into two letrozole groups (100 or 200 μg/d) and a control group (placebo). Both letrozole doses resulted in increased body weight, inguinal fat accumulation, anovulation, larger ovaries with follicular atresia and multiples cysts, endogenous hyperandrogemia, and lower estrogen levels. Moreover, rats that received 200 μg/d had insulin resistance and enlarged adipocytes in inguinal and mesenteric fat depots, increased circulating levels of LH, decreased levels of FSH, and increased ovarian expression of Cyp17a1 mRNA. Thus, continuous administration of letrozole, 200 μg/d, to female rats for 90 d starting before puberty results in a PCOS model with reproductive and metabolic features of the syndrome.


Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 943-952
Author(s):  
Noha M. Shawky ◽  
Chetan N. Patil ◽  
Carolina Dalmasso ◽  
Rodrigo O. Maranon ◽  
Damian G. Romero ◽  
...  

Polycystic ovary syndrome, the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, obesity, insulin resistance, and elevated blood pressure. However, few studies have focused on the consequences of pregnancy on postmenopausal cardiovascular disease and hypertension in polycystic ovary syndrome women. In hyperandrogenemic female (HAF) rats, the hypothesis was tested that previous pregnancy protects against age-related hypertension. Rats were implanted with dihydrotestosterone (7.5 mg/90 days, beginning at 4 weeks and continued throughout life) or placebo pellets (controls), became pregnant at 10 to 15 weeks, and pups were weaned at postnatal day 21. Dams and virgins were then aged to 10 months (still estrous cycling) or 16 months (postcycling). Although numbers of offspring per litter were similar for HAF and control dams, birth weights were lower in HAF offspring. At 10 months of age, there were no differences in blood pressure, proteinuria, nitrate/nitrite excretion, or body composition in previously pregnant HAF versus virgin HAF. However, by 16 months of age, despite no differences in dihydrotestosterone, fat mass/or lean mass/body weight, previously pregnant HAF had significantly lower blood pressure and proteinuria, higher nitrate/nitrite excretion, with increased intrarenal mRNA expression of endothelin B receptor and eNOS (endothelial nitric oxide synthase), and decreased ACE (angiotensin-converting enzyme), AT1aR (angiotensin 1a receptor), and endothelin A receptor than virgin HAF. Thus, pregnancy protects HAF rats against age-related hypertension, and the mechanism(s) may be due to differential regulation of the nitric oxide, endothelin, and renin-angiotensin systems. These data suggest that polycystic ovary syndrome women who have experienced uncomplicated pregnancy may be protected from postmenopausal hypertension.


2018 ◽  
Vol 44 (1) ◽  
pp. 10
Author(s):  
Ana Janaina Jeanine Martins de Lemos-Jordão ◽  
Fabiano Sellos Costa ◽  
Christina Alvez Peixoto ◽  
Álvaro Aguiar Coelho Teixeira ◽  
Solange Bezerra da Silva ◽  
...  

Background: Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder, results in menstrual abnormalities, androgynism and infertility. In the case of women or others animals with PCOS wishing to treat infertility with the aim of becoming pregnant, the most commonly used is metformin hydrochloride. Recent studies have analyzed the combination of metformin hydrochloride with melatonin in oncological treatment but not to treatment of polycystic ovary syndrome (PCOS). The aim of the present study was to analyze the effectiveness of the combination of metformin hydrochloride and melatonin in the treatment of PCOS to improve the fertility of rats and your hormonal alterations.Materials, Methods & Results: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Federal Rural of Pernambuco (Permit Number: 23081.009130/2010). A total of 50 albino Wistar rats were used. The animal laboratory of an academic research environment, were randomly separated into five groups consisting of 10 females each. After inducing PCOS, the rats were treated with metformin hydrochloride, and/or melatonin, and the results compared with standard and ultrasound confirmed. The physiological similarities were confirmed by our academic researchers morphological science, and published to the association results of effects syndrome induction through constant lighting in reputable magazine recently. This article was analyzed histological of the implantation sites and ovaries, and the estradiol and progesterone levels on the seventh day of gestation, and the other rats for monitoring pregnancy and morphological identification of possible fetal abnormalities, weight measurement and quantification of offspring. The rats were anaesthetized with intraperitoneal injections of ketamine hydrochloride (80 mg/kg) and xylazine (6 mg/kg) to allow analysis of the reproductive organs. Main outcome measures: The study included histopathology, histochemical and quantitative (of the implantation sites) tests, ultrasound analysis, weight benchmarking and ovarian histology tests, as well as comparison of serum estradiol and progesterone levels, and the morphological assessment of offspring. Results paper shows pharmacological treatment reduced the time needed for pregnancy, increased the plasma progesterone levels, the number and weight of offspring, and reduced plasma estrogen levels and collagen fiber grade, improving blastocyst-endometrium interaction and fetal development.Discussion: Our team of researchers confirmed in a previous paper; in addition, the main experimental model used in research about PCOS in recent years, and considered appropriate combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the POS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. The treatment with a combination of metformin hydrochloride and melatonin was more effective against hormonal alterations produced by PCOS, allowing a normalization of biochemical parameters during pregnancy, than monotherapeutic treatment with these drugs. In conclusion, proposed drug combination is a viable option to treatment of polycystic ovary syndrome and improved fetal development. This article allows suggest that further research should be conducted to examine effects associated with these drugs in the treatment of diseases of the female reproductive system experimentally. Only such treatment later in animals and humans suggest.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Mohammed Azeemuddin ◽  
Suryakanth D. Anturlikar ◽  
Mallappa Onkaramurthy ◽  
Mirza R. Baig ◽  
Basti K. Ashok ◽  
...  

The objective of the present study was to evaluate “DXB-2030,” a polyherbal combination of Trigonella foenum-graecum, Aloe vera, Sphaeranthus indicus, Nardostachys jatamansi, and Symplocos racemosa extracts in an experimental model of testosterone propionate (TP), induced polycystic ovary syndrome (PCOS) in female rats. Thirty animals were divided into 3 groups of 10 each; group 1 served as normal control; group 2 was administered with TP and served as positive control; along with TP, group 3 was treated with “DXB-2030” at a dose of 100 mg/kg p.o., for 60 days. At the end of the study period, the animals were subjected for the estimation of serum testosterone levels, oral glucose tolerance test (OGTT), weight of the ovaries, estrous cycle, and histopathological evaluation. An in vitro assay on GLUT4 expression was carried out to understand the effect of “DXB-2030” on insulin resistance. Results showed that treatment with “DXB-2030” reversed the TP-induced changes by increasing the GLUT4 expression and decreasing the body weight, testosterone levels, AUC of glucose in OGTT, and the cystic follicles of the ovaries, thus indicating its beneficial effect in PCOS by ameliorating the metabolic dysfunction and reproductive impairment, which are the pathophysiological conditions associated with PCOS. From the results obtained, it can be concluded that “DXB-2030” was effective in the management of experimental PCOS and hence may be recommended in the treatment of PCOS.


Author(s):  
Zora Lazúrová ◽  
Jana Figurová ◽  
Beáta Hubková ◽  
Jana Mašlanková ◽  
Ivica Lazúrová

Abstract Objectives There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. Methods Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. Results PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. Conclusions PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.


2020 ◽  
Vol 9 (6) ◽  
pp. 1831
Author(s):  
Elena Khashchenko ◽  
Elena Uvarova ◽  
Mikhail Vysokikh ◽  
Tatyana Ivanets ◽  
Lyubov Krechetova ◽  
...  

Relevance: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. Design: A case-control study. Methods: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17α-OH progesterone (17α-OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). Results: The serum levels of LH (9.0 (5.4–13.8) vs. 3.7 (2.5–4.7) IU/L; p < 0.0001), LH/FSH (1.6 (1.0–2.3) vs. 0.7 (0.5–1.1); p < 0.0001), 17α–OHP (4.1 (3.2–5.1) vs. 3.4 (2.7–3.8) nmol/L; p = 0.0071), cortisol (464.0 ± 147.6 vs. 284.0 ± 129.7 nmol/L; p < 0.0001), prolactin (266.0 (175.0–405.0) vs. 189.0 (142.0–269.0) mIU/L; p = 0.0141), T (1.9 (1.2–2.5) vs. 0.8 (0.7–1.1) nmol/L; p < 0.0001), androstenedione (15.8 (11.6–23.2) vs. 8.3 (6.5–10.8) ng/mL; p < 0.0001), AMH (9.5 (7.5–14.9) vs. 5.8 (3.8–6.9) ng/mL; p < 0.0001), FAI (5.5 (2.8–7.0) vs. 1.6 (1.1–2.3); p < 0.0001), SHBG (37.0 (24.7–55.5) vs. 52.9 (39.0–67.6) nmol/L; p = 0.0136), DHEAS (6.8 ± 3.2 vs. 5.1 ± 1.5 μmol/L; p = 0.0039), and leptin (38.7 ± 27.1 vs. 23.7 ± 14.0 ng/mL; p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level > 7.20 ng/mL, FAI > 2.75, androstenedione > 11.45 ng/mL, total T > 1.15 nmol/L, LH/FSH ratio > 1.23, and the volume of each ovary > 10.70 cm3 (for each criterion sensitivity ≥ 75.0–93.0%, specificity ≥ 83.0–93.0%). The diagnostic accuracy of PCOS determination was 90.2–91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 − (1.73 × AMH) − (0.12 × Leptin)] was less than 70.72. Conclusions: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents.


2011 ◽  
Vol 23 (4) ◽  
pp. 520 ◽  
Author(s):  
Yun Liu ◽  
Hong Jiang ◽  
Ling-Yun He ◽  
Wu-Jian Huang ◽  
Xiao-Yu He ◽  
...  

Polycystic ovary syndrome (PCOS) may result from hypersensitivity to insulin, which is negatively regulated by uncoupling protein (UCP)-2. Because cholesterol side-chain cleavage enzyme (CYP11A1) is closely linked to PCOS, the expression of UCP-2 and CYP11A1 in ovarian tissues from PCOS patients was examined in the present study. Twelve PCOS patients with hyperandrogenaemia who underwent laparoscopic ovarian wedge resection and 12 age-matched control patients who underwent contralateral ovarian biopsy were enrolled in the study. UCP-2 expression in early stage (primordial, primary and secondary) and late stage (sinus and mature) follicles was examined using immunohistochemistry, whereas UCP-2 and CYP11A1 mRNA and protein levels in ovarian tissue were determined using quantitative reverse transcription–polymerase chain reaction and western blot analyses, respectively. UCP-2 expression increased significantly with follicular development in both control and PCOS tissue, with expression in early stage follicles from PCOS patients significantly greater than that in controls. In addition, both UCP-2 and CYP11A1mRNA and protein levels, mean fasting blood glucose concentrations and fasting serum insulin levels were significantly higher in PCOS patients compared with the control group. Finally, a significant correlation between UCP-2 and CYP11A1 expression was found in PCOS but not control patients. In conclusion, in PCOS patients, there was a correlation between UCP-2 and CYP11A1 expression, which was significantly higher than in the control group. These changes in UCP-2 and CYP11A1 expression may mediate follicle development in PCOS.


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