Attenuation of glomerular filtration barrier damage in adriamycin-induced nephropathic rats with bufalin: an antiproteinuric agent.
Proteinuria is an important risk factor for the progression and prognosis of chronic kidney disease. Bufalin, a cardiotonic steroid, has been shown to posses a variety of biological activities including cardiotonic, anaesthetic and antineoplastic activities, and regulate the immune response. This study investigated the effects of bufalin against proteinuria and glomerular filtration barrier damage in rats with adriamycin (ADR)-induced nephropathy. We compared the blood and urine biochemical indices and the histologic and ultrastructure of the glomerulus in ADR rats with and without the intervention of bufalin or prednisone. The transcription, expression and distribution of the podocyte-associated molecules were compared utilising RT-PCR, western blotting and immunohistochemical staining. We found that bufalin reduced the urinary protein excretion and optimised the lipidaemia of the ADR rats. Bufalin alleviated the removal of podocyte foot processes and attenuated the changes in nephrin, podocin and integrin-linked kinase (ILK) stainings in the glomerulus of the ADR rats. Bufalin notably decreased the expression of nephrin and ILK but inhibited the down-regulation of podocin in protein levels on the renal cortex of the ADR rats. Additionally, bufalin inhibited the up-regulation of podocin and ILK in mRNA levels but did not affect nephrin mRNA levels. These results suggest that bufalin could alleviate ADR-induced proteinuria by protecting the glomerular filtration barrier and may be a novel potential therapeutic agent for proteinuria-associated kidney disease.
Department of Paediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210003, PR China.
Jun
J
Zheng
Jing
J
Gong
Aiqing
A
Zhang
Shanwen
S
Li
Zhifeng
Z
Zeng
Ying
Y
Han
Weihua
W
Gan
D000818:Animals; D002018:Bufanolides / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004317:Doxorubicin; D005786:Gene Expression Regulation / Q000187:drug effects; D060730:Glomerular Filtration Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011241:Prednisone / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099200:Scaffold Protein ILK
D002018:Bufanolides; D002316:Cardiotonic Agents; D004317:Doxorubicin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011241:Prednisone; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C407223:NPHS2 protein; C113267:nephrin; C022777:bufalin