Quantitative Systems Toxicology Modeling of Cisplatin Nephrotoxicity Using in vitro Assays of Proximal Tubule Epithelial Cells for Mechanistic Toxicity Pathways

Authors: Gebremichael Y, Hamzavi N, Woodhead JL, Tallapaka SB, Siler SQ, Howell BA
Conference: SOT
Keywords: Acute kidney injury (AKI), in vitro, live stream learning, mitochondrial dysfunction, oxidative stress, QST modeling
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Background

Cisplatin-induced nephrotoxicity results in acute kidney injury (AKI) and is caused by various cellular mechanisms, including mitochondrial dysfunction, oxidative stress, and others.
• AKI mechanisms of cisplatin and several other nephrotoxic drugs remain incompletely understood.
• Quantitative system toxicology (QST) offers promise for better understanding of drug induced AKI through mechanistic representation of the underlying toxicity pathways.
• We developed a QST model of cisplatin induced AKI using in vitro assay data to characterize injury pathways.

By Yeshitila Gebremichael, Nader Hamzavi, Jeffrey L. Woodhead, Shailendra Tallapaka, Scott Q. Siler, and Brett A. Howell

Canceled: SOT 59th Annual Meeting & ToxExpo March 15-19. 2020 in Anaheim, California