Acetaminophen, a new tool to refine experimental infectious processes: the case of murine toxoplasmosis

Over the past few years, animal welfare has taken more place in society and especially in scientific research. It has become necessary to refine the experimental procedures as much as possible in infectiology as in our reference model, toxoplasmosis, in agreement with the 3Rs rule and different ethical concerns. Thus, the establishment of a treatment using analgesics would relieve animals acutely infected with Toxoplasma gondii . However, the use of this analgesic should in no way alter the pathophysiology of the disease and the immune response of the host, so as not to interfere with the initial scientific study. Currently, little is known about the use of acetaminophen in an infectious model. In the present work, we studied the impact of acetaminophen at a reference dose of 30 mg/kg/day in a murine model of acute toxoplasmosis. To do this, zoonotic, telemetric, behavioral, histological and immune parameters were analyzed to better characterize the consequences of a treatment with acetaminophen either via gavage or via self-medication in Gel Water. Acetaminophen administered by gavage did not induce cellular or tissue toxicity and did not alter the physiological development of mice either. Moreover, the very nature of Gel Water, independently of APAP, has had an impact on the immune response. The acetaminophen improved the general well-being and slowed down the appearance of clinical signs without modifying the physiopathology or the immune responses induced by T. gondii . These first results in mice validated our initial hypothesis that acetaminophen appears to be a pharmacological tool to refine and improve animal welfare during the acute phase of toxoplasmosis. Therefore, our project has highlighted the combination of specific markers to contribute to animal welfare in mice. In the long term, the use of acetaminophen could be extended to other infectious models with other target animal species.