Protective Effects of Dimedone Pyrone on Podocytes in Rats with Diabetic Nephropathy

Purpose: To investigate the effect of dimedone pyrone (DP) on podocytes in rats with diabetic nephropathy (DN).
Methods: The rats were randomly assigned into 5 experimental groups (n = 10), viz, non-diabetic control with no treatment (ND/NT), diabetic with no treatment (DG/NT), diabetic treated with 5 mg/kg dimedone pyrone (DG/DP 5), diabetic treated with 10 mg/kg dimedone pyrone (DG/DP 10) and diabetic treated with 20 mg/kk dimedone pyrone (DG/DP 20) group. Clinical parameters, including 24 h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCR), blood glucose (GLU), and kidney weight (KW)/body weight (BW) were determined after 12 weeks of treatment. Hematoxylin and eosin staining was used to examine renal pathological changes while transmission electron microscopy (TEM) was employed for evaluation of structural changes in the podocytes. The expression levels of nephrin and podocin were evaluated using immunofluorescence staining.
Results: Dimedone pyrone caused a significant decrease in SCR, BUN, GLU, KW/BW and 24 h urine protein in DG/DP 20 group compared to DG/NT group. Furthermore, incidences of glomerular disorders, chronic tubulo-interstitial damage and glomerular podocyte lesions decreased significantly following dimedone pyrone treatment. Glomeruli, tubules and podocytes exhibited pathomorphological improvements while nephrin and podocin protein expression levels were significantly higher in the nephridial tissue. Decrease in relative kidney weight (KW/BW) and 24 h urinary protein level were improved significantly on treatment with dimedone pyrone. Moreover, glomerular disorder, chronic tubulo-interstitial damage and glomerular podocyte lesions were also suppressed. The improvement was more significant in DG/DP 20 compared to DG/DP 5 and DG/DP 10 groups.
Conclusion: Dimedone pyrone exhibits a protective effect on the podocytes of rats and may be of therapeutic importance in the treatment of diabetic nephropathy.

Keywords
Dimedone pyrone; Podocin; Diabetic neuropathy; Nephrin; Glomerular disorders