The poloxamer 407 induced hyperlipidemic rat model and its effect on renal toxicity of calcineurin inhibitors

  • Author / Creator
    Chaudhary, Hetal R
  • The present study characterized poloxamer 407 (P407) induced hyperlipidemia in rats and investigated its effect of on renal toxicity of the immunosuppressants tacrolimus and cyclosporine A. P407 (0.5 or 1 g/kg) was injected in rats and blood samples were collected at different time-points. Serum levels of total cholesterol, triglyceride, high-density lipoprotein (HDL), adiponectin, leptin and TNF-α were measured. In vitro renal toxicity studies were performed using LLC-PK1 and NRK-52E cells for tacrolimus and cyclosporine A, respectively. P407 increased serum cholesterol, triglyceride and HDL with maximum increase at 36h. Moreover, P407 significantly increased leptin and decreased adiponectin but did not affect TNF-α. Hyperlipidemic serum treated cells did not show any significant difference in toxicity compared to normo-lipidemic serum treated cells for both the drugs. Together, P407 induces hyperlipidemia and alters lipid and adipokine levels. Furthermore, hyperlipidemic serum treatment had no apparent effect on in vitro kidney cell toxicity by immunosuppressants.

  • Subjects / Keywords
  • Graduation date
    Fall 2012
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Specialization
    • Pharmaceutical Sciences
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Baker, Glen (Psychiatry and Centre for Neuroscience)
    • Brocks, Dion (Pharmacy and Pharmaceutical Sciences)
    • El-Kadi, Ayman (Pharmacy and Pharmaceutical Sciences)
    • Seubert, John (Pharmacy and Pharmaceutical Sciences)