CD38 inhibitor apigenin and inflammation.
Purpose of the experiment: to examine in mice if the CD38 inhibitor apigenin can suppress the inflammatory response induced by mono-sodium urate (MSU). The mice will be injected i.p. with apigenin or a control substance, and with MSU or a control substance. We hope to reduce the inflammatory response in the mice which are injected with apigenin and MSU.
Expected distress for the animals: the mice will receive two i.p. injections with either apigenin/control substance and MSU/control substance (mild), and blood samples (mild) will be obtained. However, as analgesia is not compatible with the research set up, as we investigate the inflammatory response and analgesia will dampen this, the overall score is moderate.
Expected scientific or societal benefit: the research outcome will help us to better understand the role of CD38 plays in immune response and unravel the potential treatment effects of apigenin in inflammatory diseases.
How many and what kind of animals to be used: 108 mice in the total experiment. 96 C57Bl6/J mice and 12 NLRP3 KO mice on a C57Bl6/J background.
Replacement, reduction and refinement: We started of this research project with studying the effect of apigenin in in vitro models. However, to test the actual hypothesis after these initial experiments we are depending on a mouse model. Furthermore, we have experience with the peritoneal lavage procedure and as a result we are able to predict the number of mice needed for this experiment. Aditionally, to minimize the numbers of mice needed, all participants will be trained before the start of this study by the specialist in our department to assure that variation and drop out of animals are as low as possible. Lastly, as the mice will be handled by the same, trained researchers, we assume to reduce stress, and we follow the guidelines for housing and environmental enrichment applicable to our department.
Expected distress for the animals: the mice will receive two i.p. injections with either apigenin/control substance and MSU/control substance (mild), and blood samples (mild) will be obtained. However, as analgesia is not compatible with the research set up, as we investigate the inflammatory response and analgesia will dampen this, the overall score is moderate.
Expected scientific or societal benefit: the research outcome will help us to better understand the role of CD38 plays in immune response and unravel the potential treatment effects of apigenin in inflammatory diseases.
How many and what kind of animals to be used: 108 mice in the total experiment. 96 C57Bl6/J mice and 12 NLRP3 KO mice on a C57Bl6/J background.
Replacement, reduction and refinement: We started of this research project with studying the effect of apigenin in in vitro models. However, to test the actual hypothesis after these initial experiments we are depending on a mouse model. Furthermore, we have experience with the peritoneal lavage procedure and as a result we are able to predict the number of mice needed for this experiment. Aditionally, to minimize the numbers of mice needed, all participants will be trained before the start of this study by the specialist in our department to assure that variation and drop out of animals are as low as possible. Lastly, as the mice will be handled by the same, trained researchers, we assume to reduce stress, and we follow the guidelines for housing and environmental enrichment applicable to our department.