| First Author | Korrapati MC | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 9 | Pages | e73655 |
| PubMed ID | 24040012 | Mgi Jnum | J:206049 |
| Mgi Id | MGI:5547693 | Doi | 10.1371/journal.pone.0073655 |
| Citation | Korrapati MC, et al. (2013) Suramin: a potential therapy for diabetic nephropathy. PLoS One 8(9):e73655 |
| abstractText | OBJECTIVE: To determine whether delayed administration of a single dose of suramin, a drug that has been used extensively in humans to treat trypanosomiasis, attenuates renal injury in a leptin receptor deficient C57BLKS/J db/db type 2 diabetic nephropathy (T2DN) mouse model. RESEARCH DESIGN AND METHODS: Groups of female non-diabetic (control) db/m and diabetic db/db mice of 8 and 16 weeks of age, respectively, were treated with suramin (10 mg/kg) or saline i.v. All animals were euthanized one week later. Measurements in mice 1 week following treatment included the following: body weight; blood glucose; urinary protein excretion; pathological lesions in glomeruli and proximal tubules; changes in protein expression of pro-inflammatory transcription factor nuclear factor kappaB (NF-kappaB) and intracellular adhesion molecule-1 (ICAM-1), profibrotic transforming growth factor-beta1 (TGF-beta1), phospho-SMAD-3 and alpha-smooth muscle actin (alpha-SMA); and immunohistochemical analysis of leukocyte infiltration and collagen 1A2 (COL1A2) deposition. RESULTS: Immunoblot analysis revealed increased NF-kappaB, ICAM-1, TGF-beta1, phospho-SMAD-3, and alpha-SMA proteins in both 9 and 17 week db/db mice as compared to db/m control mice. Immunohistochemical analysis revealed moderate leukocyte infiltration and collagen 1A2 (COL1A2) deposition in 9 week db/db mice that was increased in the 17 week db/db mice. Importantly, suramin significantly decreased expression of all these markers in 9 week db/db mice and partially decreased in 17 week db/db mice without altering body weight, blood glucose or urinary protein excretion. There was no difference in creatinine clearance between 9 week db/m and db/db mice +/- suramin. Importantly, in the 17 week db/db mice suramin intervention reversed the impaired creatinine clearance and overt histological damage. CONCLUSIONS: Delayed administration of a single dose of suramin in a model of T2DN attenuated inflammation and fibrosis as well as improved renal function, supporting the use of suramin in T2DN. |
