NON-PURINE SELECTIVE XANTHINE OXIDASE INHIBITOR AMELIORATES GLOMERULAR ENDOTHELIAL INJURY IN InsAkita DIABETIC MICE.

In this study, we investigated the contribution of XO activation on the progression of diabetic nephropathy (DN) in a mouse model using selective XO inhibitors. Male Ins2Akita heterozygous mice were used with wild-type (WT) mice as controls. Akita mice were treated with Topiroxostat (Topi) or vehicle for 4 weeks. Serum uric acid levels were significantly reduced in Akita+Topi compared with Akita+Vehicle mice. The Akita + Topi group had significant reduction in the urinary albumin excretion in comparison with the Akita + Vehicle group. Mesangial expansion, glomerular collagen IV deposition, and glomerular endothelial injury (assessed by lectin staining and transmission electron microscopy) were considerably reduced in the Akita + Topi group compared with the Akita + Vehicle group. Furthermore, glomerular permeability was significantly higher in the Akita + Vehicle group compared to the WT group. These changes were reduced with the administration of Topi. We conclude that XO inhibitors preserve glomerular endothelial functions and rescue compromised glomerular permeability, suggesting that XO activation plays a vital role in the pathogenesis of DN. PMID: 32954851 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research