Mercury affects uterine myogenic activity even without producing any apparent toxicity in rats: Involvement of calcium-signaling cascades |
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| Institution: | 1. Institut d’Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;2. CIBER Epidemiología y Salud Pública (CIBERESP), Spain;3. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil;4. Epidemiology and Environmental Health Joint Research Unit, FISABIO – Universitat Jaume I – Universitat de València, Valencia, Spain;1. Department of Nutritional Sciences, Tohto University, 4-2-7 Kamishibachonishi, Fukaya, Saitama 366-0052, Japan;2. Department of Nutritional Sciences, Faculty of Human Ecology, Yasuda Women’s University, Hiroshima 731-0153, Japan;3. Department of Human Nutrition, Seitoku University Graduate School, Matsudo, Chiba 271-8555, Japan;1. Department of Anatomy, Faculty of Basic medical Sciences, College of Medicine, Alex Ekwueme Federal University Ndufu-Alike Ikwo (AE-FUNAI), Ebonyi State, P.M.B. 1010, Nigeria;2. Department of Anatomy, Faculty of Basic medical Sciences, University of Nigeria Enugu Campus (UNEC), Enugu State, Nigeria;1. Instituto de Toxicología de la Defensa, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain;2. Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, Spain;3. Servicio de Ginecología, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain;4. Departamento de Bioquímica, Universidad Alcalá de Henares, Spain;1. Pfizer Worldwide Research and Development, Drug Safety R&D, One Burtt Road, Andover, MA 01810, USA;2. Pfizer Worldwide Research and Development, Drug Safety R&D, Eastern Point Road, Groton, CT 06340, USA |
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| Abstract: | BackgroundMercury is an established environmental toxicant reported to cause reproductive disorders in women, however, its direct action on myometrial activity is yet to be understood. Earlier we have reported the underlying mechanism of mercury-induced myometrial contractions following in vitro exposure; however, no such information on the effect of mercury on myometrial activity following in vivo exposure is available, therefore, the present study was undertaken.ObjectivePresent study was designed to evaluate the effect of mercury on myometrial activity following in vivo exposure of rats and unravel the possible underlying mechanism.MethodsFemale Wistar rats were orally exposed to mercury (5, 50 and 500 μg/L in drinking water) for 28 days to investigate the toxicodynamics of mercuric chloride (HgCl2)-induced alterations in myometrial activity. Response of the isolated myometrial strips to different spasmogens was recorded using polyphysiograph. Blood and uterine calcium, mercury, iron and zinc levels were estimated by atomic absorption spectrophotometry. Blood biochemicals and serum hormonal profiles (estradiol, progesterone) were also determined.ResultsNo systemic toxicity of mercury was observed in any of the treatment groups (5, 50 and 500 μg/L) in terms of alterations in body weight, organ weights, blood biochemical parameters including hormonal profile. Interestingly, mercury at 5 μg/L concentration significantly increased the receptor-dependent (PGF2α-induced) and receptor-independent (CaCl2-induced and high K+-depolarizing solution-induced) myometrial contractions and it was coupled with corresponding increase in the uterine calcium levels. However, mercury at higher dose levels (50 and 500 μg/L) did not significantly alter the myometrial response.ConclusionOur results evidently suggest that mercury at low level (5 μg/L) produced detrimental effect on myometrial activity by altering calcium entry into the smooth muscle and/or the release of calcium from intracellular stores without causing any apparent systemic toxicity in rats. |
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| Keywords: | Mercury Calcium Uterine smooth muscle Dose-dependent toxicity |
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