Pakistan Journal of Biological Sciences1028-88801812-5735Asian Network for Scientific Information10.3923/pjbs.2021.780.789Saeed AlghamdiYoussef 72021247Background and Objective: Hyperuricemia is one of the most dangerous threats to human life. It is mainly associated with gout and inflammatory arthritis. Therefore, finding a safe medication that does not have severe side-effects is a goal shared by most physicians. The current study aimed to evaluate the effect of lesinurad (Zurampic; ZUR) and allopurinol (ALP), both alone or in combination, on the treatment of hyperuricemic mice at the biochemical, molecular and cellular levels. Materials and Methods: Lesinurad and allopurinol were orally administered to hyperuricemic and control mice for seven consecutive days, either alone or in combination. Levels of uric acid and xanthine oxidase activity, blood urea nitrogen, creatinine, ALT and AST were measured in the serum. The mRNA expression of mouse hepatic guanine deaminase (Gda), purine nucleotide phosphorylase (PNP), renal urate anion transporter-1 (URAT-1) and OAT-1 transporters were examined. The renal tissues were examined using H and E staining and the immunoreactivity technique. Results: Lesinurad and allopurinol administration resulted in a significant decrease in serum levels of uric acid, blood urea nitrogen and xanthine oxidase activity reported in hyperuricemic mice. Both partially reversed oxonate-induced alterations in renal mURAT-1 and mOAT-1 expressions, as well as alterations in the immunoreactivity of Bcl2. All showed an increase in renal uric acid secretion and excretion. ALP and ZUT significantly decreased the increase in Gda and PNP expression reported in hyperuricemic mice. The combined administration of ZUR and ALP restored and improved renal function histopathological changes reported in hyperuricemic mice. Conclusion: The hypouricemic impact of both lesinurad and allopurinol in the treatment of hyperuricemia in mice was confirmed following hyperuricemia treatment.]]>Maiuolo, J., F. Oppedisano, S. Gratteri, C. Muscoli and V. Mollace,2016213814Zgaga, L., E. Theodoratou, J. Kyle, S.M. Farrington and F. Agakov et al.,20122012Chaudhary, K., K. Malhotra, J. Sowers and A. Aroor,20133208220Rock, K.L., H. Kataoka and J.J. Lai,201391323Jalal, D.I., M. Chonchol, W. Chen and G. Targher,201361134146de Oliveira, E.P. and R.C. Burini,20122012Li, L., C. Yang, Y. Zhao, X. Zeng, F. Liu and P. Fu,20142014Aung, T., G. Myung and J.D. FitzGerald,201711795800Lapi, F., L. Azoulay, H. Yin, S.J. Nessim and S. Suissa,20132013Beydoun, M.A., M.T. Fanelli-Kuczmarski, J.A. Canas, H.A. Beydoun, M.K. Evans and A.B. Zonderman,2018120935945Choi, H.K., K. Atkinson, E.W. Karlson, W. Willett and G. Curhan,200435010931103Benn, C.L., P. Dua, R. Gurrell, P. Loudon, A. Pike, R.I. Storer and C. Vangjeli,20182018Desaulniers, P., M. Fernandes, C. Gilbert, S.G. Bourgoin ad P.H. Naccache,200170659668Terkeltaub, R.,201063038Knake, C., L. Stamp and A. Bahn,2014452157162Soliman, M.M., M.A. Nassan, A. Aldhahrani, F. Althobaiti and W.A. Mohamed,2020Petroselinum crispum and Apium graveolens against experimental hyperuricemia.]]>2020Sattui, S.E. and A.L. Gaffo,20168145159Xin, Y., K. Wang, Z. Jia, T. Xu and Q. Xu et al.,20184710741083Pérez-Ruiz, F., T. Jansen, A.K. Tausche, M. Juárez-Campo, K.G. Ravichandra and P. Richette,20198111Enomoto, A., H. Kimura, A. Chairoungdua, Y. Shigeta, P. Jutabha and S.H. Cha et al.,2002417447452Huneycutt, E., C. Board and J.N. Clements,201731670677Hoy, S.M.,201676509516Alghamdi, Y.S., M.M. Soliman and M.A. Nassan,20202020Wu, T., J. Chen, S. Dong, H. Li and Y. Cao et al.,20176911031112Soliman, M.M., A. Aldhahrani, A. Alkhedaide, M.A. Nassan, F. Althobaiti and W.A. Mohamed,2020Moringa oleifera leaf extract against oxidative stress and methotrexate-induced hepato-renal dysfunction.]]>2020Cicero, A.F.G., F. Fogacci, M. Kuwabara and C. Borghi,20212021Farquhar, H., A.B. Vargas-Santos, H.L. Pisaniello, M. Fisher, C. Hill, A.L. Gaffo and L.K. Stamp,20212021Li, L., Y. Zhang and C. Zeng,20201231673181Kuwabara, M.,20163242252Nuki, G. and P.A. Simkin,20062006Wang, M.X., Y.L. Liu, Y. Yang, D.M. Zhang and L.D. Kong,20157475970Di Giovine, F.S., S.E. Malawista, G. Nuki and G.W. Duff,198713832133218Terkeltabu, R.,2006648286Mahor, D. and G.S. Prasad,2018Kluyveromyces lactis adenine deaminase and guanine deaminase and their potential application in lowering purine content in beer.]]>2018Jacomelli, G., E. Baldini, C. Mugnaini, V. Micheli, G. Bernardini and A. Santucci,2019in vitro studies with analogues of immucillin‐G.]]>42178185Otani, N., M. Ouchi, K. Hayashi, P. Jutabha and N. Anzai,201792200206