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Abstract
Summary & Conclusion.1;
Summary & Conclusions This study was earned out in two stages, stage I, the animal
model study in 36 New Zealand While rabbits to observe the deleterious
effect of induced hyperlipidemia, CsA and Sirolimus. Stage II in liver transplant recipients to asses the relationship between ROS activity,CYP3A4 enzymatic activity, and the different type of irnmunosuppressantto the cardiovascular events.2)Administration of CsA alone in rabbits did not induce significantchange in fasting blood glucose level. While, administration of SRL alone
deceased fasting blood glucose significantly.3)Neither CsA nor SRL alone induced significant changes in thelipid profile.4)CsA or SRL had no effect on liver enzymes except for the serumalbumin which decrease with the administration of both CsA and SRL in rabbits.5)There was no nephroioxic effect demonstrated in the rabbitstreated with cither of CsA or SRL measured by scrum creatinine.ft) Both CsA and SRL induced oxidative stress as demonstrated by the elevated MDA levels in the serum, liver and aorta. Additionally, we concluded that the level of the inflammatory mediators during SRL therapy is higher when compared with CsA. Thus, we believe that immunosuppressive therapy increases cardiovascular risk factors in humans at least in part due to enhancement of the ROS activity as seen in the animal model. Furthermore, the level of oxidative stress induced by the immunosuppressive therapy is different among the different agents as seen between CsA and SRL7 SRL significantly decreased CYP3A4 enzymes activity.