Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 44, Issue 6, Pages 830-837Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b21-00036
Keywords
chemotherapy; acute kidney injury; panduratin A; human renal proximal tubule; anti-apoptosis
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Funding
- International Research Network (IRN), Thailand Research Funds [IRN5804PHDW02]
- Thailand Science Research and Innovation [RSA6280082]
- Central Instrument Facility (CIF), Faculty of Science, Mahidol, University
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Panduratin A demonstrates nephroprotective effects on cisplatin-induced renal injury by reducing apoptosis in both mice and human renal cell cultures. It does not alter the intracellular accumulation of cisplatin and does not impact the anti-cancer efficacy of cisplatin in cancer cell lines.
Background: Cisplatin is an effective chemotherapy but its main side effect, acute kidney injury, limits its use. Panduratin A, a bioactive compound extracted from Boesenbergia rotunda, shows several biological activities such as anti-oxidative effects. The present study investigated the nephroprotective effect of panduratin A on cisplatin-induced renal injury. Methods: We investigated the effect of panduratin A on the toxicity of cisplatin in both mice and human renal cell cultures using RPTEC/TERT1 cells. Results: The results demonstrated that panduratin A ameliorates cisplatin-induced renal toxicity in both mice and RPTEC/TERT1 cells by reducing apoptosis. Mice treated with a single intraperitoneal (i.p.) injection of cisplatin (20 mg/kg body weight (BW)) exhibited renal tubule injury and impaired kidney function as shown by histological examination and increased serum creatinine. Co-administration of panduratin A (50 mg/kg BW) orally improved kidney function and ameliorated renal tubule injury of cisplatin by inhibiting activation of extracellular signal-regulated kinase (ERK)1/2 and caspase 3. In human renal proximal tubular cells, cisplatin induced cell apoptosis by activating pro-apoptotic proteins (ERK1/2 and caspase 3), and reducing the anti-apoptotic protein (Bcl-2). These effects were significantly ameliorated by co-treatment with panduratin A. Interestingly, panduratin A did not alter intracellular accumulation of cisplatin. It did not alter the anti-cancer efficacy of cisplatin in either human colon or non-small cell lung cancer cell lines. Conclusions: The present study highlights panduratin A has a potential protective effect on cisplatin's nephrotoxicity.
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