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


Other title
Hyperlipidemia, Poloxamer 407, Cyclosporine, Tacrolimus
Type of item
Degree grantor
University of Alberta
Author or creator
Chaudhary, Hetal R
Supervisor and department
Brocks, Dion (Pharmacy and Pharmaceutical Sciences)
Examining committee member and department
El-Kadi, Ayman (Pharmacy and Pharmaceutical Sciences)
Brocks, Dion (Pharmacy and Pharmaceutical Sciences)
Baker, Glen (Psychiatry and Centre for Neuroscience)
Seubert, John (Pharmacy and Pharmaceutical Sciences)
Faculty of Pharmacy and Pharmaceutical Sciences
Pharmaceutical Sciences
Date accepted
Graduation date
Master of Science
Degree level
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.
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