Dual targeting of TNF-α and free radical toxic stress as a promising strategy to manage experimental polycystic ovary. (2nd January 2016)

• Record Type: Journal Article
• Authors: Rezvanfar, Mohammad Amin; Saeedi, Sarah; Mansoori, Parisa; Saadat, Sepideh; Goosheh, Maziar; Shojaei Saadi, Habib A.; Baeeri, Maryam; Abdollahi, Mohammad
• Is Part Of: Pharmaceutical biology. Volume 54:Number 1(2016:Jan.)
• Page Start: 80
• Page End: 90
• Publication Date: 2016-01-02
• Subjects: Beta-blockers -- herbal medicine -- hyperandrogenism -- oxidative stress; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.3109/13880209.2015.1014922
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: Context : It is now clear that oxidative stress (OS) and chronic low-grade inflammation are two main pathways involved in polycystic ovary syndrome (PCOS) pathogenesis. Therefore, simultaneous targeting of these pathways by means of carvedilol and Semelil (ANGIPARS™), as established medicines with dual anti-cytokine and anti-oxidant potential may be a therapeutic alternative approach to the current treatments. Objective : The objective of this study is to study the protective effects of carvedilol and ANGIPARS™ on inflammatory and oxidative response in hyperandrogenism-induced polycystic ovary (PCO). Materials and methods : The murine model of PCO was induced by letrozole (1 mg/kg/d; orally) and effective doses of carvedilol (10 mg/kg/d; orally) and ANGIPARS™ (2.1 mg/kg/d; orally) were administrated for 21 d in PCO and non-PCO healthy rats. Ovarian folliculogenesis, sex hormones concentrations, OS, inflammatory, and metabolic biomarkers were assessed in serum and ovaries. Results : PCO rats exhibited ovarian cystogenesis which was preserved by the application of carvedilol and ANGIPARS™. In comparison with controls, decreased level of the total antioxidant power (TAP) and higher levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in serum and ovaries (2.41 ± 0.67 versus 0.72 ± 0.11; and 0.17 ± 0.04 versus 0.05 ± 0.01; 5.48 ± 1.30 versus 10.56 ± 0.77; and 7.06 ± 1.94 versus 17.98 ± 0.98; p < 0.05, respectively) were detected in PCO rats. Moreover, the PCO rats exhibited hyperandrogenism due to a 3.7-fold increase in serum testosterone concentration (35.04 ± 3.17 versus 131.09 ± 13.24; p < 0.05) along with a 2.98-fold decrease in serum progesterone (6.19 ± 0.40 versus 18.50 ± 1.03; p < 0.05) and 5.2-fold decrease in serum estradiol (9.30 ± 0.61 versus 48.3 ± 2.10; p < 0.05) when compared with those of the control group. However, similar to the control group, normal levels of OS markers and sex hormones were detected in ANGIPARS™ and carvedilol co-treated PCO rats. Besides, when compared with controls, increased levels of TNF-α (770.75 ± 42.06 versus 477.14 ± 28.77; p < 0.05) and insulin (1.27 ± 0.10 versus 0.36 ± 0.05; p < 0.05) in PCO rats were significantly inhibited by carvedilol and ANGIPARS™ co-treatment. Discussion and conclusion : We evidenced the beneficial effects of carvedilol and ANGIPARS™ in PCO, which underpin the new alternative approach in using these kinds of medicines in female reproductive disorders.