Date on Master's Thesis/Doctoral Dissertation

8-2025

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

Clark, Geoff

Author's Keywords

Nephrotoxicity; oncology; onconephrology; kidney; AKI; CKD

Abstract

Cisplatin is a potent chemotherapeutic, thirty percent of patients develop Acute Kidney Injury (AKI). These patients are ten times more likely to develop chronic kidney disease (CKD). Sodium-glucose-cotransporter-2-inhibitors (SGLT2i), FDA approved for diabetes, has shown protection in multiple mouse models of AKI-CKD. We hypothesize SGLT2i can protect the kidney in a model of repeated low dose cisplatin with/without cancer. B6:129 mice with/without lung adenocarcinoma (Lung-adeno) were treated daily with SGLT2i dapagliflozin (10mg/kg)/vehicle control. After seven days, weekly cisplatin (7mg/kg)/vehicle control was initiated for 3-4 weeks. Following final cisplatin dose, kidney function, injury, fibrosis, inflammation was assessed. SGLT2i treatment attenuated alterations in kidneys of mice without Lung-adeno. SGLT2i treatment didn’t prevent alterations in kidney in mice with Lung-adeno. SGLT2i didn’t alter tumor growth/response to cisplatin. Results suggest SGLT2i provide partial protection from cisplatin induced AKI-CKD in mice without Lung-adeno, these effects are nullified in mice with Lung-adeno.

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