| 20139407 |
Sanchez-Pozos K, Lee-Montiel F, Perez-Villalva R, Uribe N, Gamba G, Bazan-Perkins B, Bobadilla NA: Polymerized type I collagen reduces chronic cyclosporine nephrotoxicity. Nephrol Dial Transplant. 2010 Feb 5.
BACKGROUND: Polymerized type I collagen (P-collagen) has been successfully used to reduce human hypertrophic scars due to its anti-fibrotic and anti-inflammatory properties. We therefore carried out a study to determine if P-collagen reduces functional and structural injury in chronic cyclosporine [cyclosporine A (CsA)] nephropathy. METHODS: Four groups of six male Wistar rats fed with a low sodium diet were treated with vehicle, P-collagen (0.8 mg/day, i.p.), CsA (15 mg/kg) or CsA + P-collagen for 15 days. Mean arterial pressure, renal blood flow and glomerular filtration rate were measured in all groups. Structural injury such as arteriolopathy, tubulo-interstitial fibrosis (TI-fibrosis) and positive apoptotic cells were quantified. The mRNA expression levels of transforming growth factor-beta (TGF-beta), kidney injury molecule (Kim-1), alpha-smooth muscle actin (alpha-SMA), glutathione peroxidase, catalase and Cu/Zn superoxide dismutase (SOD) as well as MnSOD were assessed. Antioxidant enzyme activity, renal lipoperoxidation and urinary excretion of oxygen peroxide (UH (2) O (2) V) were determined. RESULTS: Cyclosporine produced renal dysfunction and induced the development of arteriolopathy, TI-fibrosis and tubular apoptosis. These alterations were associated with increases in TGF-beta, Kim-1 and alpha-SMA mRNA levels as well as with a significant increase of oxidative stress and a reduction of SOD activity. P-Collagen partially ameliorated CsA-induced renal dysfunction and structural injury and prevented both tubular apoptosis and increased oxidative stress. This renoprotective effect was found to be associated with a reduction of TGF-beta, Kim-1 and alpha-SMA mRNA levels. CONCLUSIONS: This study has therefore demonstrated that P-collagen appears to have anti-fibrotic and anti-apoptotic properties and highlights the possibility that the compound might be useful in a strategy to reduce chronic CsA nephrotoxicity. |
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