الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The present study was conducted to investigate effects of the single and combined oral administration of the selective ROCK inhibitor, fasudil and the angiotensin receptor blocker, valsartan on the vascular and renal complications in streptozotocin (STZ) induced diabetic rats.
Our results showed that administration of STZ caused a marked elevation of serum creatinine, urea, and increased albumin-creatinine ratio (ACR). This was associated with upregulated aortic and renal TNF-, NADPH oxidase subunit NOX2, and Rho/ ROCKa activity and protein levels, detected by western blot analysis alongside increased reactive oxygen species (ROS) production and decreased antioxidant enzyme activity. The single or combined administration of fasudil or valsartan could significantly decrease the elevation of serum creatinine, urea, and increased albumin-creatinine ratio (ACR). In addition, administration of fasudil individually or in its dual combination with valsartan could TNF-, NADPH oxidase subunits NOX2 and p45phox, and Rho/ ROCKa activity and protein levels. Furthermore, this was associated with a marked attenuated in the progression of aortic or renal histological abnormalities of diabetic rats.
In the light of these findings, it is reasonable to postulate that activation of TNF-α/ROCK axis through induction of NADPH oxidase-driven oxidative stress plays an important role in the pathology of diabetic nephropathy. Thus our study suggest that this multidrug approach as a strategy for combating the oxidative stress along with inhibition the renal expression of TGF-, and TNF-α thereby improving renal function and pathology in diabetic nephropathy.