Renoprotective and in silico Modeling Studies of Febuxostat in Gentamicin Induced Nephrotoxic Rats

Ali Alqahtani, Kumarappan Chidambaram, Khalid Asseri, Krishnaraju Venkatesan, Absar Ahmed Qureshi, Afaf Aldahish, Taha Alqahtani, Yahia Alghazwani, Talha Bin Emran, Hesham M. Hassan, Saeed A. Asiri, Noohu Abdulla Khan and Pitchai Balakumar

Background and Objective: Febuxostat is used for the treatment of hyperuricemia that improves renal function in CKD patients, but its renal protective effect has not been fully studied. This study has been undertaken to evaluate the potential modulatory effects of febuxostat on renal dysfunction and kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. Materials and Methods: These effects were assessed in terms of analysing biochemical (creatinine, urea, blood urea nitrogen, uric acid, serum electrolytes, alanine aminotransferase, aspartate transaminase and alkaline phosphatase, among others) parameters, total histological kidney score, as well as the histological assay of kidney and liver tissues. Results: As compared to gentamicin control (100 mg kg^–1) groups, the febuxostat (10 mg kg^–1, i.p.) pre/post-treatment was significantly preventive in terms of biochemical parameters and the total histological score of kidney tissue. Either pre/post-treatment markedly reduced the changes of glomerular enlargement, degeneration tubular hyaline casts and tubular degeneration, while the liver showed no remarkable changes in hepatocytes or liver architecture. Conclusion: This observation may have a great impact on the use of aminoglycosides, whereas febuxostat may have a key potential to prevent the associated renal toxicity induced by the administration of gentamicin.

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