| First Author | Zhou Y | Year | 2011 |
| Journal | Kidney Int | Volume | 79 |
| Issue | 12 | Pages | 1302-11 |
| PubMed ID | 21368746 | Mgi Jnum | J:186870 |
| Mgi Id | MGI:5433446 | Doi | 10.1038/ki.2011.17 |
| Citation | Zhou Y, et al. (2011) Peroxisome proliferator-activated receptor-alpha is renoprotective in doxorubicin-induced glomerular injury. Kidney Int 79(12):1302-11 |
| abstractText | Doxorubicin (DOX) is an anthracycline antibiotic utilized in antitumor therapy; however, its clinical use is frequently impeded by renal toxic effects. As peroxisome proliferator-activated receptor-alpha (PPAR-alpha) has renoprotective effects in drug-related kidney injuries, we tested its ability to inhibit DOX-induced renal injury. Although both male PPAR-alpha knockout mice and their wild-type littermates (pure 129/SvJ background) had significant proteinuria 4 weeks after DOX treatment, those with deletion of PPAR-alpha had more severe proteinuria. This was associated with more serious podocyte foot process effacement compared with wild-type mice. In contrast, the PPAR-alpha agonist fenofibrate effectively reduced proteinuria and attenuated DOX-induced podocyte foot process effacement. Consistently, glomerular nephrin expression was significantly lower in the knockout compared with wild-type mice following DOX treatment. Fenofibrate therapy significantly blunted the reduction in glomerular nephrin levels in DOX-treated wild-type mice. In cultured podocytes, DOX induced apoptosis, increased cleaved caspase-3 levels, and decreased Bcl-2 expression, all attenuated by pretreatment with fenofibrate. Thus, PPAR-alpha deficiency exacerbates DOX-related renal injury, in part, due to increased podocyte apoptosis. |
