Publication: Panduratin a derivative protects against cisplatin-induced apoptosis of renal proximal tubular cells and kidney injury in mice
Issued Date
2021-11-01
Resource Type
ISSN
14203049
Other identifier(s)
2-s2.0-85118556076
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecules. Vol.26, No.21 (2021)
Suggested Citation
Penjai Thongnuanjan, Sirima Soodvilai, Somsak Fongsupa, Natechanok Thipboonchoo, Napason Chabang, Bamroong Munyoo, Patoomratana Tuchinda, Sunhapas Soodvilai Panduratin a derivative protects against cisplatin-induced apoptosis of renal proximal tubular cells and kidney injury in mice. Molecules. Vol.26, No.21 (2021). doi:10.3390/molecules26216642 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/75978
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Panduratin a derivative protects against cisplatin-induced apoptosis of renal proximal tubular cells and kidney injury in mice
Other Contributor(s)
Abstract
Background: Panduratin A is a bioactive cyclohexanyl chalcone exhibiting several pharmacological activities, such as anti-inflammatory, anti-oxidative, and anti-cancer activities. Recently, the nephroprotective effect of panduratin A in cisplatin (CDDP) treatment was revealed. The present study examined the potential of certain compounds derived from panduratin A to protect against CDDP-induced nephrotoxicity. Methods: Three derivatives of panduratin A (DD-217, DD-218, and DD-219) were semi-synthesized from panduratin A. We investigated the effects and corresponding mechanisms of the derivatives of panduratin A for preventing nephrotoxicity of CDDP in both immortalized human renal proximal tubular cells (RPTEC/TERT1 cells) and mice. Results: Treating the cell with 10 µM panduratin A significantly reduced the viability of RPTEC/TERT1 cells compared to control (panduratin A: 72% ± 4.85%). Interestingly, DD-217, DD-218, and DD-219 at the same concentration did not significantly affect cell viability (92% ± 8.44%, 90% ± 7.50%, and 87 ± 5.2%, respectively). Among those derivatives, DD-218 exhibited the most protective effect against CDDP-induced renal proximal tubular cell apoptosis (control: 57% ± 1.23%; DD-218: 19% ± 10.14%; DD-219: 33% ± 14.06%). The cytoprotective effect of DD-218 was mediated via decreases in CDDP-induced mitochondria dysfunction, intracellular reactive oxygen species (ROS) generation, activation of ERK1/2, and cleaved-caspase 3 and 7. In addition, DD-218 attenuated CDDP-induced nephrotoxicity by a decrease in renal injury and improved in renal dysfunction in C57BL/6 mice. Importantly, DD-218 did not attenuate the anti-cancer efficacy of CDDP in non-small-cell lung cancer cells or colon cancer cells. Conclusions: This finding suggests that DD-218, a derivative of panduratin A, holds promise as an adjuvant therapy in patients receiving CDDP.