Refining drug administration in a murine model of acute infection with Trypanosoma cruzi
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Laboratory Animal Research
METHODOLOGY
Open Access
Refining drug administration in a murine model of acute infection with Trypanosoma cruzi Julián Ernesto Nicolás Gulin1,2* , Margarita Bisio1,2 and Facundo García-Bournissen1,2
Abstract Background: In animal research, “refinement” refers to modifications of husbandry or experimental procedures to enhance animal well-being and minimize or eliminate pain and distress. Evaluation of drug efficacy in mice models, such as those used to study Trypanosoma cruzi infection, require prolonged drug administration by the oral route (e.g. for 20 consecutive days). However, the orogastric gavage method can lead to significant discomfort, upper digestive or respiratory tract lesions, aspiration pneumonia and even accidental death. The aim of this work was to evaluate the effect of two administration methods (conventional oral gavage vs. a refined method using a disposable tip and automatic pipette) on the efficacy of benznidazole in a murine model of T. cruzi infection. Results: Both administration methods led to a rapid and persistent reduction in parasitaemia. Absence of T. cruzi DNA (evaluated by real-time PCR) in blood, cardiac and skeletal muscle confirmed that treatment efficacy was not influenced by the administration method used. Conclusions: The proposed refined method for long-term oral drug administration may be a suitable strategy for assessing drug efficacy in mice models of Chagas disease and can be applied to similar murine infection models to reduce animal discomfort. Keywords: Chagas disease animal models, Chronic treatment - Oral administration, Preclinical drug research, Refinement
Background Drug administration by the oral route is a common method to achieve systemic exposure. Substances can be delivered to the gastrointestinal tract by including them in water or food, by oropharyngeal administration of capsules, pills or fluids, or through gavage [1] requiring physical restraint by trained staff to minimize animal harm and stress.
* Correspondence: [email protected] 1 Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), Hospital de Niños “Dr. Ricardo Gutiérrez”, CONICET- GCBA, Gallo 1330, 1425 Buenos Aires, Argentina 2 Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños “Dr. Ricardo Gutiérrez”. Ministerio de Salud. GCBA, Buenos Aires, Argentina
When a research protocol requires chronic oral drug administration, inclusion in food or water may be possible, but may increase variability and uncertainty in the ingested dose, reducing dosing accuracy. In addition, many compounds are not water-soluble, and environmental conditions such as temperature and humidity can affect stability [2]. Oral gavage delivers a known drug amount in a single administration step. Though effective, it requires substantial technical skills, is very labor-intensive and is not suitable for long-term and/or frequent treatments. Disadvantages of gavage dosing include risks of esophageal or stomach damage and inadvertent administration int
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