Date on Master's Thesis/Doctoral Dissertation

12-2019

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Siskind, Leah

Committee Co-Chair (if applicable)

Beverly, Levi

Committee Member

Beverly, Levi

Committee Member

Clark, Geoff

Committee Member

Lederer, Eleanor

Committee Member

Yaddanapudi, Kavitha

Author's Keywords

Cisplatin; neutral ceramidase; acute kidney injury; chronic kidney disease

Abstract

Cisplatin is a commonly used chemotherapeutic agent with a dose-limiting nephrotoxicity. 30% of patients given cisplatin develop acute kidney injury (AKI). AKI increases risk of chronic kidney disease (CKD) development and mortality. Patients that don’t develop clinical AKI are still at risk for long term declines in renal function. Currently, there are no FDA approved agents to treat or prevent cisplatin-induced kidney injury (CDDP-KI). In this study, we demonstrated that neutral ceramidase (nCDase) knockout provides protection from AKI in the high-dose model of CDDP-KI. However, in the repeated low dose cisplatin (RLDC) model of injury and we found nCDase knockout does not prevent development of CKD. We also observed that nCDase knockout reduces induction of ER stress in the single high-dose model but not in the RLDC model. This study suggests there are unique mechanisms of RLDC induced kidney injury which may have hindered development of nephroprotective agents.

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