Date on Master's Thesis/Doctoral Dissertation

8-2016

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Siskind, Leah

Committee Member

Beverly, Levi

Committee Member

Arteel, Gavin

Committee Member

Lederer, Eleanor

Committee Member

Clark, Geoff

Author's Keywords

nephrotoxicity; cisplatin; fibrosis; kidney; AKI; CKD

Abstract

Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have developed a repeated dosing model of cisplatin (7mg/kg once a week for four weeks). This model allows for the long-term survival of mice, and the associated pathology is fibrosis-the hallmark of CKD. Thus, data indicate that the repeated dosing model can be used to study AKI to CKD progression.

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