<scp>d</scp> ‐Alanine Hydrochloride and <scp>d</scp> ‐Alanine Dipeptide Have Biological Activity and Promote Human Proximal Tubular Epithelial Cell Viability
Acute kidney injury (AKI) remains a significant clinical challenge with limited therapeutic options. While d-alanine shows promise in AKI treatment, its formulation requires l-alanine co-inclusion for pharmaceutical stabilization through racemization. This study investigated the biological activity of synthetic d-alanine compounds in the human proximal tubular epithelial cell line (HK-2). We synthesized d-alanine hydrochloride, a dipeptide, and a tripeptide and evaluated their effects on cell viability under normal and hypoxic conditions. d-Alanine hydrochloride (10 µM) and dipeptide (10 µM) significantly enhanced cell viability compared with the controls, with d-alanine hydrochloride demonstrating superior efficacy under hypoxic conditions. Gene expression analysis revealed that these compounds promoted cell cycle progression and increased cyclin B1 expression under hypoxic conditions. Notably, these synthetic forms maintained therapeutic efficacy without requiring l-alanine co-inclusion. Although limited to in vitro experiments, our findings suggest that d-alanine hydrochloride and dipeptide forms are promising therapeutic candidates for AKI treatment.
Authors
- Ryo Nishioka (ORCID: https://orcid.org/0000-0001-8654-7311)
- Yasunori Iwata (ORCID: https://orcid.org/0000-0002-4756-5207)
- Yusuke Nakade (ORCID: https://orcid.org/0000-0002-0094-359X)
- Masashi Mita
- Akira Tamai
- Akihiko Koshino (ORCID: https://orcid.org/0000-0002-9432-2427)
- Keisuke Sako (ORCID: https://orcid.org/0000-0002-8272-5085)
- Keisuke Horikoshi
- Kyoko Nakagawa‐Goto (ORCID: https://orcid.org/0000-0002-1642-6538)
- Taichiro Minami
- Megumi Oshima (ORCID: https://orcid.org/0000-0002-4108-5229)
- Kiyoaki Ito (ORCID: https://orcid.org/0000-0002-1818-3525)
- Ichiro Mizushima (ORCID: https://orcid.org/0000-0002-6231-0683)
- Hoang Thuy Linh (ORCID: https://orcid.org/0000-0001-7860-5219)
- Norihiko Sakai (ORCID: https://orcid.org/0000-0001-7245-9716)
- Miho Shimizu (ORCID: https://orcid.org/0000-0002-7737-935X)
- Takahiro Yuasa (ORCID: https://orcid.org/0009-0004-3556-935X)
- Akinori Hara (ORCID: https://orcid.org/0000-0002-0399-1474)
- Takashi Wada
- Yohei Saito (ORCID: https://orcid.org/0000-0003-2313-8339)
- Shunsuke Tsuge
Institutions
- Kanazawa University (JP)
- University of North Carolina at Chapel Hill (US)
- Kasumigaura Medical Center (JP)
- Kagami Crystal (Japan) (JP)
Publication Details
- Journal
- Chemistry & Biodiversity
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1002/cbdv.202501108
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science