title: Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats.
abstract: OBJECTIVE
  Recent studies have shown that the inflammatory process is involved in the pathogenesis of diabetic nephropathy. Fourteen-membered ring macrolides, including erythromycin, have anti-inflammatory, as well as antibacterial effects. The aim of this study was to investigate the renoprotective effects of erythromycin in streptozotocin (STZ)-induced diabetic rats.
  
  
  METHODS
  STZ-induced diabetic rats were treated orally with erythromycin (5 mg/kg body weight) or vehicle every day for 8 weeks. To evaluate the effect of erythromycin treatment, we measured urinary albumin excretion, and examined the following in the kidney: histological changes, the expression of intercellular adhesion molecule-1 (ICAM-1), macrophage infiltration, and nuclear factor-kappa B (NF-kappaB) activity.
  
  
  RESULTS
  Erythromycin significantly reduced urinary albumin excretion without affecting blood glucose levels and blood pressure. Erythromycin also attenuated glomerular hypertrophy, mesangial expansion, macrophage infiltration and ICAM-1 expression in renal tissues. The expression of the gene encoding TGFB1 (also known as TGF-beta1), type IV collagen protein production and NF-kappaB activity in renal tissues were increased in diabetic rats and reduced by erythromycin treatment.
  
  
  CONCLUSIONS
  Erythromycin prevented renal injuries without changes of blood glucose levels and blood pressure in experimental diabetic rats. These results suggest that the renoprotective effects of erythromycin are based on its anti-inflammatory effect via suppression of NF-kappaB activation. Modulation of microinflammation with erythromycin may provide a new approach for diabetic nephropathy.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tone
authors.forename: K
authors.initials: K
authors.lastname: Shikata
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: S
authors.initials: S
authors.lastname: Ohga
authors.forename: K
authors.initials: K
authors.lastname: Yozai
authors.forename: S
authors.initials: S
authors.lastname: Nishishita
authors.forename: H
authors.initials: H
authors.lastname: Usui
authors.forename: R
authors.initials: R
authors.lastname: Nagase
authors.forename: D
authors.initials: D
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Shikata
authors.forename: J
authors.initials: J
authors.lastname: Wada
authors.forename: H
authors.initials: H
authors.lastname: Makino
mesh_terms: D000419:Albuminuria / Q000188:drug therapy; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000187:drug effects / Q000235:genetics; D024141:Collagen Type IV / Q000187:drug effects / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004917:Erythromycin / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008264:Macrophages / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics; D053773:Transforming Growth Factor beta1
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D024141:Collagen Type IV; D016328:NF-kappa B; C508962:Tgfb1 protein, rat; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; D013311:Streptozocin; D004917:Erythromycin