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X-ray analysis of the effect of the 5-HT3 receptor antagonist granisetron on gastrointestinal motility in rats repeatedly treated with the antitumoral drug cisplatin

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Abstract

Cancer chemotherapy is associated with the development of numerous adverse effects, including nausea, emesis and other alterations in gastrointestinal (GI) motility. The administration of 5-HT3 receptor antagonists has provided a clinical advance in the treatment of chemotherapy-induced vomiting but these drugs lose efficacy throughout chronic treatment. The effects of these drugs in experimental animals under chronic administration are not well known. Our aim was to study, using radiographic methods, the effect of the 5-HT3 receptor antagonist granisetron on GI dysmotility induced in the rat by repeated cisplatin administration. First, invasive methods were used to select a dose of granisetron capable of reducing increased stomach weight due to acute cisplatin administration (6 mg/kg, ip). Second, rats received two intraperitoneal (ip) injections once a week for 4 weeks: granisetron (1 mg/kg, ip) or saline and, thirty min later, saline or cisplatin (2 mg/kg, ip). Body weight gain was measured throughout treatment. Radiological techniques were used to determine the acute (after first dose) and chronic (after last dose) effects of cisplatin and/or granisetron on GI motility. Repeated cisplatin-induced weight loss which granisetron did not prevent. Gastric emptying was delayed after the first cisplatin administration. Granisetron completely prevented this effect. After weekly administration, cisplatin-induced gastric dysmotility was enhanced and granisetron was not capable of completely preventing this effect. Granisetron prevents gastric emptying alterations, but its efficacy decreases throughout antineoplastic treatment. This might be due to the enhanced effect of cisplatin.

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Acknowledgments

This work was supported by Ministerio de Educación y Ciencia (SAF2009-12422-C02-01; SAF2012-40075-C02-01), Universidad Rey Juan Carlos—Comunidad de Madrid (URJC-CM-2006-BIO-0604), Comunidad de Madrid (S2010/BMD-2308) and Fundación Mapfre (Ayudas a la Investigación-Promoción de la Salud 2011: Alimentación y Ejercicio Físico). The authors are grateful to Maica Merino, Guadalupe Pablo and Iván Álvarez for their technical assistance. The Department of Pharmacology and Nutrition is Unidad Asociada I + D + i del Consejo Superior de Investigaciones Científicas (CSIC).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departamento de Farmacología y Nutrición, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, 28922, Alcorcón, Madrid, Spain

    Gema Vera, María Martínez-Villaluenga, Pablo Antonio Cabezos & Raquel Abalo

  2. Unidad del Dolor, Servicio de Anestesiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Ana Esther López-Pérez

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  1. Gema Vera
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  2. Ana Esther López-Pérez
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Correspondence to Raquel Abalo.

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Vera, G., López-Pérez, A.E., Martínez-Villaluenga, M. et al. X-ray analysis of the effect of the 5-HT3 receptor antagonist granisetron on gastrointestinal motility in rats repeatedly treated with the antitumoral drug cisplatin. Exp Brain Res 232, 2601–2612 (2014). https://doi.org/10.1007/s00221-014-3954-5

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