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Tuesday, December 2, 2025
8:00 am ET / 22:00 JST / 13:00 UTC

Hiroshi Arakawa, PhD, Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University

ABSTRACT: Acute kidney injury was caused by exposure to chemicals, including drugs, which significantly affects patient health and prognosis. Drug-induced acute kidney injury is frequently observed in proximal tubule because renal proximal tubular epithelial cells (RPTECs) have abundant expression of drug transporters¹. Therefore, reliable risk assessment methodologies for drug-induced proximal tubular injury are essential. Although chemical-induced nephrotoxicity has been evaluated using experimental animals, concerns about animal welfare and limited human relevance highlight the need for useful New Approach Methodologies (NAMs). Our research group found that the expression levels of various drug transporters including OAT1 were increased in spheroidal cultured human RPTECs (3D-RPTECs)², and that changes in intracellular ATP levels could be used as an indicator to assess drug-induced proximal tubular injury with high predictive performance³. We conducted a domestic pre-validation study of the cytotoxicity test using the intracellular ATP levels to examine the robustness of the evaluation system, and obtained high inter-laboratory reproducibility. Moreover, we have focused on a confocal imaging analysis that can evaluate functional changes in organelles such as mitochondria after drug exposure. In addition, we investigated proximal tubular injury by puberulic acid, a contaminant of red yeast rice supplement⁴. Collectively, our findings indicate that 3D-RPTEC not only provides mechanistic insights into drug-induced proximal tubular injury but also has potential as a versatile tool for broader chemical safety evaluation.

References

1) Arakawa et al., Drug Metab Pharmacokint, 61:101056 (2025).
2) Ishiguro et al., Drug Metab Dispos, 51:1177–87 (2023).
3) Arakawa et al., J Pharm Sci, 113:3255–64 (2024).
4) Peng et al., Biol Pharm Bull, 48:928–31 (2025).

ABOUT THE PRESENTER
Dr. Hiroshi Arakawa is a professor in the Department of Regulatory Science at Nagoya City University Graduate School of Pharmaceutical Sciences.  He holds a PhD, MS, and BS all in pharmacokinetics.  His research and ongoing work include construction and development of biomimetic models for drug safety assessment; drug side effects and drug-drug interactions via drug transporters; elucidation of mechanisms involved in pharmacokinetics and safety using clinical data; and elucidation of dynamics and physiological effects of uremic toxins.

Recordings and other materials from this webinar will be posted to the ASCCT webinar archive: https://www.ASCCTox.org/Webinar-Archive