Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Committee Co-Chair (if applicable)
Cisplatin; kidney; AKI; CKD; PGC-1α
Cisplatin is highly effective and one of the most commonly used chemotherapeutic agents in the treatment of a number of different solid organ tumors. Unfortunately, the dose-limiting nephrotoxicity occurs in up to 30% of patients, which requires alterations to treatment regimens that are often less effective. The kidney’s function is to provide fluid homeostasis, and this is an energy-intensive process. Proper renal function is dependent on functional mitochondria. PGC-1α regulates mitochondrial number, respiratory capacity, and mitochondrial proteins in proximal tubule cells. We delivered low-dose cisplatin to mice via intraperitoneal injections once a week for 4 weeks. The mice were then euthanized, and the kidneys were immediately extracted and frozen. Our data show that repeated dosing of cisplatin results in reduced renal function, increased fibrosis, reduced mitochondrial content, and reduced PGC-1α in kidney cortices. We hypothesize that increasing PGC-1α will protect against cisplatin-induced kidney injury.
Orwick, Andrew Joseph, "Decreased kidney mitochondrial content and PGC-1α following repeated low-dose cisplatin-induced kidney injury." (2021). Electronic Theses and Dissertations. Paper 3673.