2. Academic Validation
  3. Evaluation of Drug-Induced Kidney Injury by Primary Culture of Rat Kidney Tissue Slices Using Oxygen-Permeable Polyolefin Plate with Low Drug Adsorption

Evaluation of Drug-Induced Kidney Injury by Primary Culture of Rat Kidney Tissue Slices Using Oxygen-Permeable Polyolefin Plate with Low Drug Adsorption

  • Biol Pharm Bull. 2026;49(1):122-129. doi: 10.1248/bpb.b25-00572.
Moeno Kadoguchi 1,  Kohei Matsushita 2,  Katsuhiro Esashika 3,  Jingjing Yang 4,  Jun Takahashi 3,  Ikumi Tamai 1,  Hiroshi Arakawa 1 5
Affiliations

Affiliations

  • 1 Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
  • 2 Division of Pathology, National Institute of Health Sciences, 3-25-26 Tono-machi, Kawasaki-ku, Kawasaki 210-9501, Japan.
  • 3 Synthetic Chemicals Laboratory, Mitsui Chemicals, Inc., 1144 Togo, Mobara, Chiba 297-0017, Japan.
  • 4 Cell Culture Solution Department, New Business Incubation Center, Mitsui Chemicals, Inc., Tokyo Midtown Yaesu, Yaesu Central Tower, 2-2-1 Yaesu, Chuo-ku, Tokyo 104-0028, Japan.
  • 5 Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
PMID: 41565252 DOI: 10.1248/bpb.b25-00572
Abstract

Rat kidney tissue slices are expected to be useful for an in vitro evaluation of drug-induced kidney injury (DIKI). We previously established a primary culture of rat kidney tissue slices using gas-permeable plates. However, polydimethylsiloxane (PDMS) exhibits a significant adsorption of lipophilic drugs, leading to limitations in DIKI evaluation. The aim of the present study was to evaluate a gas-permeable InnoCell™ non-treated plate made of polyolefin with low adsorption of lipophilic compounds for the primary culture of rat kidney tissue slices as an in vitro DIKI evaluation system. Drug concentrations in the medium were measured 24 h after the addition of 9 drugs to PDMS plates and InnoCell™ non-treated plates. Intra-tissue ATP levels and histopathology of rat kidney tissue slices were examined on Day 3 of culture. As a result, the InnoCell™ non-treated plates exhibited lower adsorption rates for sunitinib, cyclosporine A, and alectinib than the PDMS plates. Intra-tissue ATP levels were maintained, and immunohistochemical staining of megalin and Aquaporin 1 was observed for up to 3 d. Furthermore, exposure to nephrotoxic lipophilic drugs reduced the ATP content in slices compared to that in non-treated slices. These results suggest that the primary culture of rat kidney tissue slices using InnoCell™ non-treated plates is useful for the DIKI evaluation of lipophilic drugs compared with conventional PDMS plates.

Keywords

adsorption; drug-induced kidney injury; in vitro assay; kidney tissue slice; oxygen-permeable.

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