<b>Background and Objective:</b>
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. <b>Materials and Methods:</b>
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. <b>Results:</b>
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. <b>Conclusion:</b> The hypouricemic impact of both
lesinurad and
allopurinol in the treatment of
hyperuricemia in mice was confirmed following
hyperuricemia treatment.