1. Academic Validation
  2. Serum Amyloid A3 Promoter-Luciferase Reporter Mice Are Useful for Early Drug-Induced Nephrotoxicity Detection

Serum Amyloid A3 Promoter-Luciferase Reporter Mice Are Useful for Early Drug-Induced Nephrotoxicity Detection

  • Int J Mol Sci. 2024 May 8;25(10):5124. doi: 10.3390/ijms25105124.
Ayane Kudo 1 Haruka Osedo 1 Rahmawati Aisyah 1 Nao Yazawa 1 Tolulope Peter Saliu 1 Kenshu Miyata 1 Thanutchaporn Kumrungsee 1 Noriyuki Yanaka 1
Affiliations

Affiliation

  • 1 Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8528, Japan.
Abstract

Early detection of drug-induced kidney injury is essential for drug development. In this study, multiple low-dose aristolochic acid (AA) and cisplatin (Cis) injections increased renal mRNA levels of inflammation, fibrosis, and renal tubule injury markers. We applied a serum amyloid A3 (Saa3) promoter-driven luciferase reporter (Saa3 promoter-luc mice) to these two tubulointerstitial nephritis models and performed in vivo bioluminescence imaging to monitor early renal pathologies. The bioluminescent signals from renal tissues with AA or CIS injections were stronger than those from normal kidney tissues obtained from normal mice. To verify whether the visualized bioluminescence signal was specifically generated by the injured kidney, we performed in vivo bioluminescence analysis after opening the stomachs of Saa3 promoter-luc mice, and the Saa3-mediated bioluminescent signal was specifically detected in the injured kidney. This study showed that Saa3 promoter activity is a potent non-invasive indicator for the early detection of drug-induced nephrotoxicity.

Keywords

aristolochic acid; cisplatin; in vivo imaging; luciferase; nephrotoxicity; serum amyloid A3.

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