title: Acute and chronic effects of dietary sodium restriction on renal tubulointerstitial fibrosis in cisplatin-treated rats.
abstract: BACKGROUND
  Renal interstitial fibrosis is a major complication of cisplatin (CP) treatment, and increased sodium intake may accelerate its progression by stimulating transforming growth factor (TGF)-β/Smad signaling. However, it is not clear whether a low-sodium diet has beneficial effects on the development of interstitial fibrosis because it activates the renin-angiotensin-aldosterone system. Here, we tested whether the TGF-β/Smad signaling pathway is stimulated in CP-treated rats, and whether the development of tubulointerstitial fibrosis in CP nephropathy can be checked by dietary sodium restriction.
  
  
  METHODS
  Male Sprague Dawley rats were randomly divided into controls, CP treatment and CP treatment with low-sodium diet. The acute experiment lasted 7 days with a single intraperitoneal injection (6 mg/kg) of CP, and the chronic experiment involved weekly injections (2 mg/kg) for 7 weeks.
  
  
  RESULTS
  In both sets of experiments, CP treatment produced pronounced tubulointerstitial injury, increased infiltration of ED1-positive cells and increased expression of monocyte chemotactic protein-1 (MCP-1), α-smooth muscle actin (SMA), TGF-β1, phosphorylated Smad3, fibronectin and collagen III proteins. In the acute experiment, the increases in expression of osteopontin, MCP-1, α-SMA, TGF-β and collagen III were significantly reduced by dietary sodium restriction. In the chronic experiment, however, none of the measurements were improved by a low-sodium diet. Examination of CP-treated rat kidneys revealed de novo vimentin expression in tubular epithelial cells and invasion of α-SMA-positive tubular epithelial cells through the basement membrane into the interstitium.
  
  
  CONCLUSIONS
  The pro-fibrotic effect of TGF-β in CP nephropathy appears to be associated with the epithelial-mesenchymal transition and is ameliorated by dietary sodium restriction only during the acute phase.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Joon-Sung
authors.initials: JS
authors.lastname: Park
authors.forename: Chor Ho
authors.initials: CH
authors.lastname: Jo
authors.forename: Sua
authors.initials: S
authors.lastname: Kim
authors.forename: Gheun-Ho
authors.initials: GH
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002908:Chronic Disease; D002945:Cisplatin / Q000633:toxicity*; D004039:Diet, Sodium-Restricted / Q000009:adverse effects*; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D002945:Cisplatin