Cisplatin is a powerful chemotherapeutic agent extensively used in the management of various cancers. However, cisplatin induces significant nephrotoxicity, hence limiting its clinical applications. Exosomes are nanosized extracellular vesicles that contain various biomolecules (such as proteins, lipids, nucleic acids, and non-coding RNA) and play an important role in intercellular communication. There has been increasing interest in the potential of plant-derived exosomes as therapeutic agents due to their excellent biocompatibility, minimal side effects, and diverse bioactive ingredients. This study investigates the protective effect of onion-derived exosome (Onion-Exo) on cisplatin-induced cytotoxicity in human renal proximal tubular epithelial cells (hPTECs).

An in vitro assay was performed in hPTECs with 5, 10, and 20 µg/mL Onion-Exo and cytotoxicity was induced by 25 µM cisplatin.

Onion-Exo is safe for non-tumorous human cells because no significant cytotoxicity was observed, even at a high concentration. Onion-Exo reversed the decrease in hPTECs viability induced by cisplatin in a dose-dependent manner. A minimum concentration of malondialdehyde (MDA), an indicator of lipid peroxidation, was noted in untreated cells, but an elevated MDA level was identified in cisplatin-treated cells. However, this increase in MDA was diminished when these cells were co-incubated with Onion-Exo, suggesting that Onion-Exo could reduce cisplatin-induced oxidative stress in renal epithelial cells. The enhanced expression levels of cleaved caspase-3, phosphorylated p65, and secreted IL-6 induced by cisplatin were significantly attenuated by Onion-Exo treatment, indicating that Onion-Exo ameliorates cisplatin-induced injury in hPTECs by antagonizing apoptosis, oxidative stress, and inflammation.

Our data demonstrated for the first time that Onion-Exo could counteract cisplatin-induced damages in renal proximal tubular epithelial cells in vitro. While additional molecular investigations, animal experiments, and clinical trials are still needed, our study provides evidence of the clinical potential of Onion-Exo in cisplatin-based cancer therapies with reduced cytotoxicity.