title: Suramin: a potential therapy for diabetic nephropathy.
abstract: 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.
  
  
  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 κB (NF-κB) and intracellular adhesion molecule-1 (ICAM-1), profibrotic transforming growth factor-β1 (TGF-β1), phospho-SMAD-3 and alpha-smooth muscle actin (α-SMA); and immunohistochemical analysis of leukocyte infiltration and collagen 1A2 (COL1A2) deposition.
  
  
  RESULTS
  Immunoblot analysis revealed increased NF-κB, ICAM-1, TGF-β1, phospho-SMAD-3, and α-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.
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Midhun C
authors.initials: MC
authors.lastname: Korrapati
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Howell
authors.forename: Lauren H
authors.initials: LH
authors.lastname: Howell
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Shaner
authors.forename: Judit K
authors.initials: JK
authors.lastname: Megyesi
authors.forename: Leah J
authors.initials: LJ
authors.lastname: Siskind
authors.forename: Rick G
authors.initials: RG
authors.lastname: Schnellmann
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000737:chemistry; D016328:NF-kappa B / Q000378:metabolism; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics; D051900:Smad3 Protein; D013498:Suramin / Q000494:pharmacology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology
chemical_list: D000199:Actins; D024042:Collagen Type I; D016328:NF-kappa B; D054411:Receptors, Leptin; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1; D014344:Trypanocidal Agents; C515447:leptin receptor, mouse; D018799:Intercellular Adhesion Molecule-1; D013498:Suramin
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