Hepatic and Renal Impacts of Lesinurad on Experimental Hyperuricemia: Biochemical, Molecular and Pathological Investigations

Youssef Saeed Alghamdi

Background 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.

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