Dual targeting of TNF-α and free radical toxic stress as a promising strategy to manage experimental polycystic ovary.

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.