title: Combinatorial effects of quercetin and sex-steroids on fluid and electrolytes' (Na+, Cl-, HCO3-) secretory mechanisms in the uterus of ovariectomised female Sprague-Dawley rats.
abstract: Dysregulation of uterine fluid environment could impair successful reproduction and this could be due to the effect of environmental estrogens. Therefore, in this study, effect of quercetin, an environmental estrogen on uterine fluid and electrolytes concentrations were investigated under sex-steroid influence. Ovariectomised adult female Sprague-Dawley rats were given 10, 50 or 100mg/kg/day quercetin subcutaneously with 17-β estradiol (E) for seven days or three days E, then three days E plus progesterone (P) (E+P) treatment. Uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations were determined by in-vivo perfusion. Following sacrifice, uteri were harvested and levels of the proteins of interest were identified by Western blotting and Realtime PCR. Distribution of these proteins in the uterus was observed by immunofluorescence. Levels of uterine cAMP were measured by enzyme-linked immunoassay (EIA). Administration of quercetin at increasing doses increased uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations, but to the levels lesser than that of E. In concordant, levels of CFTR, SLC4A4, ENaC (α, β and γ), Na+/K+-ATPase, GPα/β, AC and cAMP in the uterus increased following increased in the doses of quercetin. Co-administration of quercetin with E caused uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations to decrease. In concordant, uterine CFTR, SLC26A6, SLC4A4, ENaC (α, β and γ), Na+/K+-ATPase, GPα/β, AC and cAMP decreased. Greatest effects were observed following co-administration of 10mg/kg/day quercetin with E. Co-administration of quercetin with E+P caused uterine fluid Na+ and HCO3- concentrations to increase but no changes in fluid secretion rate and Cl- concentration were observed. Co-administration of high dose quercetin (100 mg/kg/day) with E+P caused uterine CFTR, SLC26A6, AC, GPα/β and ENaC (α, β and γ) to increase. Quercetin-induced changes in the uterine fluid secretion rate and electrolytes concentrations could potentially affect the uterine reproductive functions under female sex-steroid influence.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Huma
authors.initials: H
authors.lastname: Shahzad
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Nelli
authors.initials: N
authors.lastname: Giribabu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Kamarulzaman
authors.initials: K
authors.lastname: Karim
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Normadiah M
authors.initials: NM
authors.lastname: Kassim
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, MAHSA University, Jalan Elmu, Off Jalan University, Kuala Lumpur, Malaysia.
authors.forename: Sekaran
authors.initials: S
authors.lastname: Muniandy
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Naguib
authors.identifier: http://orcid.org/0000-0002-4926-0490
authors.initials: N
authors.lastname: Salleh
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D001826:Body Fluids / Q000187:drug effects* / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D004573:Electrolytes / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D010052:Ovariectomy; D021381:Protein Transport / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D000076988:Sulfate Transporters; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D017920:Antiporters; D001639:Bicarbonates; D002712:Chlorides; D004573:Electrolytes; D053503:Epithelial Sodium Channels; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D012739:Gonadal Steroid Hormones; C579655:SLC26A6 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011794:Quercetin; D012964:Sodium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase