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

Autor: Maryam Baeeri, Habib A. Shojaei Saadi, Sepideh Saadat, Parisa Mansoori, Mohammad Amin Rezvanfar, Mohammad Abdollahi, Sarah Saeedi, Maziar Goosheh
Rok vydání: 2015
Předmět:
0301 basic medicine
Anti-Inflammatory Agents
Pharmaceutical Science
Pharmacology
medicine.disease_cause
Antioxidants
Pathogenesis
0302 clinical medicine
Drug Discovery
Gonadal Steroid Hormones
Carvedilol
030219 obstetrics & reproductive medicine
Letrozole
General Medicine
Polycystic ovary
Molecular Medicine
Drug Therapy
Combination
Female
medicine.symptom
Inflammation Mediators
medicine.drug
Polycystic Ovary Syndrome
medicine.medical_specialty
Inflammation
03 medical and health sciences
Internal medicine
Nitriles
medicine
Animals
Rats
Wistar
business.industry
Plant Extracts
Tumor Necrosis Factor-alpha
Hyperandrogenism
Ovary
Triazoles
medicine.disease
Disease Models
Animal
Oxidative Stress
030104 developmental biology
Endocrinology
Complementary and alternative medicine
Lipid Peroxidation
business
Reactive Oxygen Species
Oxidative stress
Biomarkers
Hormone
Zdroj: Pharmaceutical biology. 54(1)
ISSN: 1744-5116
Popis: 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.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).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.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; p0.05, 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; p0.05) along with a 2.98-fold decrease in serum progesterone (6.19 ± 0.40 versus 18.50 ± 1.03; p0.05) and 5.2-fold decrease in serum estradiol (9.30 ± 0.61 versus 48.3 ± 2.10; p0.05) 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; p0.05) and insulin (1.27 ± 0.10 versus 0.36 ± 0.05; p0.05) in PCO rats were significantly inhibited by carvedilol and ANGIPARS™ co-treatment.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.
Databáze: OpenAIRE
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