To evaluate the urate-lowering effect and potential drug targets of antihypertensive agent allisartan isoproxil (ALI) and its bioactive metabolite EXP3174, we developed an acute hyperuricemic zebrafish model using potassium oxonate and xanthine sodium salt. Losartan potassium served as the positive control (reference drug). In this model, ALI and losartan potassium exerted a greater urate-lowering effect than EXP3174 indicating that the latter is not the critical substance for elimination of uric acid. The quantitative real-time PCR showed that ALI upregulates the expression of intestinal urate transporters genes ABCG2, PDZK1, and SLC2A9 (p<0.01). Thus, we can suggest that this substance promotes uric acid excretion mainly by interacting with intestinal urate transporters.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 175, No. 5, pp. 574-580, May, 2023
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Xiao, Y., Miao, Z., Sun, J. et al. Allisartan Isoproxil Promotes Uric Acid Excretion by Interacting with Intestinal Urate Transporters in Hyperuricemic Zebrafish (Danio rerio). Bull Exp Biol Med 175, 638–643 (2023). https://doi.org/10.1007/s10517-023-05917-9
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DOI: https://doi.org/10.1007/s10517-023-05917-9