Document Type

Thesis

Date of Award

Spring 5-15-2013

School/College

College of Pharmacy and Health Sciences (COPHS)

Degree Name

MS Pharmaceutical Science

First Advisor

Professor Adebayo Oyekan

Abstract

mTOR has anti-inflammatory effect and inhibition of mTOR initiates IL-12 and IL-6 production leading to inflammatory response. However; it is not fully known whether mTOR activation attenuates the inflammation in renal ischemia -reperfusion (IR). We hypothesized that activation of mTOR suppresses the inflammatory response induced by IR in the kidney. The aims of the study are to characterize the role of mTOR in normal kidney function and to investigate the role of mTOR activation in IR induced kidney inflammation. In rats subjected to IR injury (25 min renal artery occlusion) in the presence or absence of rapamycin, mTOR inhibitor, or Clenbuterol, mTOR activator, markers of renal function, injury and inflammation were measured. In euvolemic anesthetized rats, Rapamycin increased blood pressure (142 ± 5 vs. 120 ± 3mmHg; p<0.05), decreased glomerular filtration rate (2 ± 0.3 to 0.6 ± 0.4 ml/min; p<0.05) and increased urinary sodium excretion (15 ± 2 vs. 107 ± 42 mlvl/hr; P<0.05).In IR rats (vehicle-treated), serum creatinine tended to increase (0.5+0.17 vs.1.3+0.1; p>0.05). 2 Rapamycin increased serum creatinine (1.3 ± 0.1 vs. 5 ± 1.6 mg/dl; p<0.05) with no significant difference in serum IL-6. Clenbuterol tended to antagonize the effect of rapamycin on serum creatinine (3.2 ± 1.6 vs. 5 ± 1.6 mg/dl; p>0.05). In conclusion, mTOR plays a role in renal injury via an IL-6 independent pathway

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