Comparative evaluation of uricodepressants allopurinol and febuxostat in gouty nephropathy. Message 2. Еxperimental study

O.V. Sinyachenko, T.B. Bevzenko, D.M. Fedorov

Abstract


Background. In our previous study (message 1), a comparative evaluation on the efficacy of two uricodepressants, allopurinol and febuxostat, was performed in terms of their effect on the functional state of the kidneys in patients with gouty nephropathy, and the advantage of the latter was established. The purpose of this study: a comparative evaluation of allopurinol and febuxostat effects on the manifestations of experimental gouty nephropathy. Materials and methods. The experiment was performed on 70 white male nonlinear rats. The animals were once injected with Freund’s complete adjuvant with splenic deoxyribonucleic acid of bovine animals and were subsequently kept on a daily diet consisted of autolyzed yeast with ammonium molybdate and inosine, and a sterile suspension of uric acid was injected into their abdominal cavities every 10 days. After 20 days, the rats were divided into 3 groups: group 1, with allopurinol added to daily nutrition; group 2 received febuxostat; group 3, which had not been treated with uricodepressants. The rats were sacrificed under inhalation ether and intraperitoneal nembutal anesthesia. The kidney tissues were examined by means of the light microscopy. Morphological preparations were stained: with hematoxylin and eosin, van Gieson’s and alcian blue, periodic ­acid-Schiff reaction was applied, the average index of the lesion of parti­cular renal structures was calculated. Results. In experimental gouty nephropathy, all kidney structures (glome­ruli, tubules, stroma, vessels) are damaged, the incidence and severity are associated with ongoing uricodepressive therapy; in addition, the xanthine oxidase inhibitor allopurinol and the xanthine oxidoreductase inhibitor febuxostat equally reduce the level of uricemia, but the effect of the former is more focused on tubulointerstitial changes, and the latter — on glomerular, followed by the inhibition of non-protein nitrogen products and medium-weight molecules in the blood. Conclusions. Taking into consideration the previous clinical study, the advantage of febuxostat over allopurinol in gouty nephro­pathy was established.


Keywords


gout; nephropathy; animal testing; allopurinol; febuxostat

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DOI: https://doi.org/10.22141/2307-1257.7.3.2018.140203

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