Rho-kinase Inhibitor,Fasudil,Attenuates Contrast-induced Acute Kidney Injury

Background Contrast-induced acute kidney injury(CI-AKI)is a serious complication of radiodiagnostic procedures.Present study was designed to assess the effects of fasudil,a Rho kinases inbibitor,on the prevention of CI-AKI,Methods Forty mice were subjected to unilateral ligation of the left anterior renal pedicle.Seven days later,animals were divided into four groups as follows(n=10):(1)control group,(2)CI-AKI induced by contrast media(CM group),(3)CI-AKI plus low dose Fasudil(LD group),and(4)CI-AKI plus high dose Fasudil(HD group).Animals from group 2-4 received iodixanol(4.0g iodine/kg),the control group received saline.At 12h,2h before injection of iodixanol and at 4h after this operation,animals in groups 2-3 respectively received 3mg/kg or 10mg/kg fasudil.Renal blood flow,renal function parameters,kidney histology,renal apoptosis,the expression of apoptosis regulatory proteins,inflammation regulatory proteins,Rho-associated protein kinase(ROCK),and the phosphorylation of myosin phosphatase target subunit-1(MYPT-1),were determined 24 hours later.Results Fasudil inhibited NF-?B p65 activation and inflammation reaction induced by CM treatment(p<0.05).However,only the high dose of fasudil treatment was shown to notably ameliorate contrast medium induced medullary damage,restore renal function,and suppress renal tubular apoptosis.Conclusion The results showed that fasudil attenuated CM-induced rise of creatinine,urea,and structural abnormalities suggesting its nephroprotective effect,which was partly attributed to its anti-inflammatory,anti-apoptotic and anti-oxidant effects by inhibiting the Rho/ROCK pathway.These findings support the use of fasudil to combat CM-induced nephrotoxicity.