Refining drug administration in a murine model of acute infection with Trypanosoma cruzi

• Published in: Laboratory animal research 2020, 36(4), , pp.356-362
• Main Authors: Gulin, Julián Ernesto Nicolás, Bisio, Margarita, García-Bournissen, Facundo
• Format: Article
• Language: English
• Subjects: Animal husbandry; Animal models; Animals; Benznidazole; Cardiac muscle; Chagas disease; Chagas disease animal models; Chemotherapy; Chronic treatment - Oral administration; Drug dosages; Infections; Methodology; Methods; Mortality; Musculoskeletal system; Oral administration; Parasitic diseases; Preclinical drug research; Protozoa; R&D; Refinement; Research & development; Respiratory tract; Skeletal muscle; Trypanosoma cruzi; 수의학
• ISSN: 1738-6055; 2233-7660; 2233-7660
• DOI: 10.1186/s42826-020-00071-z

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 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 infection. Both administration methods led to a rapid and persistent reduction in parasitaemia. Absence of DNA (evaluated by real-time PCR) in blood, cardiac and skeletal muscle confirmed that treatment efficacy was not influenced by the administration method used. 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.