title: Spironolactone and dimethylsulfoxide effect on glucose metabolism and oxidative stress markers in polycystic ovarian syndrome rat model.
abstract: Because polycystic ovarian syndrome (PCOS) is a risk factor for type 2 diabetes, the affected women can present frequently prediabetic states such as impaired fasting glycaemia and/or impaired glucose tolerance. The purpose of our study is to explore the effect of antiandrogenic spironolactone on glucose metabolism and oxidative stress (OS) parameters in oestradiol valerate (OV) induced PCOS rat model.72 female Wistar rats were distributed either to PCOS group (n=65, OV dissolved in sesame oil, 5 mg/0.4 ml), or to non-PCOS control group (n=7, sesame oil, 0.4 ml). After a month, ultrasound was performed to assess the ovarian morphology, and the results of an initial oral glucose tolerance test (OGTT) were used to identify the animals with altered glucose metabolism (AGM). Glucose transporter 4 (GLUT4) was evaluated from muscle biopsies, OS parameters were assessed from blood and muscle samples, and ovaries of 3 rats were removed for histopathological examination. Afterwards, the AGM group was divided in a treated PCOS group denoted as Sp+D (per os spironolactone dissolved in DMSO, 2 mg/0.2 ml), and a PCOS control treated with DMSO (0.2 ml). After one month of daily treatment, a final OGTT was performed. GLUT4 and OS parameters were again evaluated and ovaries were removed for histopathological examination.As compared to the values prior to the treatment, Sp+D reversed fasting hyperglycaemia (p<0.001), increased GLUT4 immunoreactivity in the perinuclear compartment (p<0.05) and translocation to plasmalemma (p<0.001) and improved superoxide dismutase (0.001<p<0.01) and glutathione peroxidase (0.001<p<0.01) activities, while reducing GSH level (0.001<p<0.01). Administration of DMSO alone decreased fasting hyperglycaemia (p<0.001) and 2-h glucose level (p<0.05) independently of GLUT4 translocation, improved superoxide dismutase (p<0.001) and glutathione peroxidase (p<0.05) activities in erythrocytes, reduced GSH level in serum (p<0.05) and diminished lipid peroxidation in muscle as compared to the values recorded before treatment (0.001<p<0.01).Our results showed that the Sp+D treatment improved antioxidant capacity and had a beneficial effect on metabolic deregulation in PCOS. Administration of DMSO had an unexpected hypoglycaemiant effect and improved OS parameters. This may represent an indirect proof of the role of oxidative stress and inflammation in PCOS and glucose metabolism abnormalities encountered in PCOS.
authors.affiliation: Department of Physiology, Iuliu Haţieganu'' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: A
authors.initials: A
authors.lastname: Dăneasă
authors.affiliation: Department of Physiology, Iuliu Haţieganu'' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: C
authors.initials: C
authors.lastname: Cucolaș
authors.affiliation: Department of Physiology, Iuliu Haţieganu'' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: M
authors.initials: M
authors.lastname: Furcea
authors.affiliation: Department of Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania.
authors.forename: P
authors.initials: P
authors.lastname: Bolfa
authors.affiliation: Department of Radiology, Iuliu Haţieganu'' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: S
authors.initials: S
authors.lastname: Dudea
authors.affiliation: Department of Physiology, Iuliu Haţieganu'' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: D
authors.initials: D
authors.lastname: Olteanu
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babeş-Bolyai University, Cluj-Napoca, Romania.
authors.forename: M C
authors.initials: MC
authors.lastname: Alupei
authors.affiliation: Department of Physiology, Iuliu Haţieganu'' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: A
authors.initials: A
authors.lastname: Mureșan
authors.affiliation: Department of Physiology, Iuliu Haţieganu'' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: G A
authors.initials: GA
authors.lastname: Filip
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007150:Immunohistochemistry; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D010053:Ovary / Q000000981:diagnostic imaging / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology*; D014463:Ultrasonography
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004232:Diuretics; D051275:Glucose Transporter Type 4; C495694:Slc2a4 protein, rat; D013148:Spironolactone; D004958:Estradiol; D005947:Glucose; D004121:Dimethyl Sulfoxide