The Role of Fasudil and Ang (1-7) in PAN Induced Nephropathy in rats | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Article 8, Volume 34, Issue 2, December 2014, Page 248-264 PDF (795.65 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2014.34795 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
| Rehab Abo El gheit; Marwa Emam | ||||
| Medical Physiology Department, Faculty of Medicine, Tanta University | ||||
| Abstract | ||||
| Background/Aim: : Nephrotic syndrome (NS) is a potentially life-threatening state characterized by heavy proteinuria, hypoalbuminemia and edema. The underlying pathological mechanisms are diverse and have not been fully elucidated. Several molecular processes have been implicated in its pathophysiology including the Rho-GTPases and renin-angiotensin (RAS) systems. We evaluated whether ROCK inhibition , through fasudil and RAS interfering through Mas agonist, AVE 0991 could have renoprotective effect, and whether it is comparable to well settled renoprotection of type-1 angiotensin II (AT1) receptor blocker, Losartan in Puromycin aminonucleoside (PAN)-induced nephropathy rat model. Materials & methods: Fifty adult male albino rats were divided into five groups (10 rats each), control (received 0.9 % NaCl). PAN- nephrotic (PAN – injected rats received 0.9 % NaCl), Fasudil treated PAN ( 30 mg/kg /d), Losartan treated PAN (10 mg/kg/ d ) and AVE 0991 treated PAN (3 mg/kg /d) group. All treated groups received treatment orally, from day 7 to day 14 of PAN injection. RESULTS: PAN injection induced marked renal dysfunction indicated by significant (P<0.05) proteinuria, hypoalbuminaemia, reduction in creatinine clearance and elevated serum creatinine associated with significant hyperlipidemia and increase in Tumor necrosis factor –α (TNF-α), C-reactive protein (C-RP) and urinary transforming growth factor -β1 (TGF-β1). Treated groups with either fasudil or AVE0991, presented with significant improvement in kidney functions and lipid profile with parallel significant reduction in inflammatory and fibrogenic cytokines that was similar to the renoprotection observed with Losartan. CONCLUSION: These data demonstrate that (RAS) and Rho-kinase pathways are involved in renal damage of NS, and their intervention could provide renoprotection and represent a novel therapy for NS. | ||||
| Keywords | ||||
| nephrotic syndrome; Nephropathy; Rho-kinase; Fasudil; Mas receptor; AVE0991; Renin-angiotensin; Losartan | ||||
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