388 Original Article
The Effects of p-nonylphenol on the Myometrial Contractile Activity
Authors
F. Yasemin Özatik1, B. Kaygısız1, K. Erol1, Y. Dündar2, T. Önkol2, M. F. Şahin3
Affiliations
1
Key words ▶ 2-hydroxy-5-nonanoyl ● benzamide ▶ isolated organ bath ● ▶ p-nonylphenol ● ▶ uterine contractility ●
received 14.01.2014 accepted 16.07.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1387717 Published online: August 27, 2014 Drug Res 2015; 65: 388–392 © Georg Thieme Verlag KG Stuttgart · New York ISSN 2194-9379 Correspondence B. Kaygısız Department of Pharmacology Faculty of Medicine Eskisehir Osmangazi University Meselik Kampusu 26480 Eskisehir Turkey Tel.: + 90/222/2392 979/4563 Fax: + 90/222/2393 772
[email protected] Department of Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Eastern Mediterranean University, Turkey 2
Abstract
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We aimed to investigate the effects and mechanisms of action of p-nonylphenol(p-NP) on uterine contractility in rats. The uterine tissues of female Sprague Dawley rats in diestrus were bathed in isolated organ bath. The effects of vehicle alone (0.1 % ethanol), the positive control 17-β-E2 (10 − 5 M) and p-NP (10 − 9 M, 10 − 8 M, 10 − 7 M, 10 − 6 M) on spontaneous and KClinduced uterine contractility of rats were studied. Also, the effects of p-NP in combination with actinomycin D (10 − 5 M) (gene transcription inhibitor), cycloheximide (10 − 4 M) (protein synthesis inhibitor), fulvestrant (10 − 6 M) (pure estrogen receptor antagonist), 2-hydroxy-5nonanoylbenzamide (10 − 3 M) (compound 1b, anti-uterotrophic compound) on spontaneous uterine contractions, and with propranolol (20 µM) (β-adrenoceptor antagonist) and noradrenaline (5 µM) on KCl (40 mM) induced
Introduction
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Estrogens, especially 17-β-estradiol (17-β-E2), have significant effects in many physiological functions such as reproduction, prevention of bone loss and cardiovascular protection [1, 2]. Both genomic and nongenomic mechanisms are involved in the effects of 17-β-E2 [3]. Genomic mechanisms implicate the binding of estrogens to nuclear receptors [4] such as estrogen receptor α and β [5]. Nongenomic actions of estrogens are more rapid than genomic actions and performed through membranal estrogen receptors [6]. There is a variety of membranal estrogen receptors such as ER46 and GPR30 mediating nongenomic actions [7, 8]. There are also substances with estrogenic actions named as xenoestrogens. Xenoestrogens are compounds that accumulate in the environment
Yasemin Özatik F et al. p-nonylphenol and Uterine Contractions … Drug Res 2015; 65: 388–392
contractions were investigated. p-NP exhibited a concentration-dependent inhibition on spontaneous uterine contractions. There was no significant difference between the highest p-NP concentration (10 − 6 M) and the positive control 17-β-E2 in terms of % inhibition (p > 0.05). The inhibitory effect of p-NP (10 − 6 M) on spontaneous contractions was blocked by actinomycin D (p