Use of PC‐NSAIDs to protect gingival cells from injury due to cytotoxic agents
Authors: Lichtenberger Lenard M. , Dial Elizabeth J. , Fang Dexing 
Published: November 2023

Background

Oral mucositis is perhaps the most severe oral side effect of cancer treatment and consists of painful inflammation and ulceration of the mucous membranes lining the oral cavity. Oral mucositis can make it difficult to eat and speak, thereby limiting the dosage and/or duration of radiation/chemotherapy, and require treatment modifications and compromises to prognosis. Antibiotic/anti‐fungal agents have limited efficacy at preventing or treating oral mucositis, also a number of “Magic Mouthwashes” that contain a variety of ingredients have not been shown to be effective, although work continues in this direction. Some other agents, such as the calcium phosphate mouth rinse Caphosol®, have shown efficacy in small clinical studies, but not been widely tested yet. Finally, due to the irritating potential on the mucosal surface any rinses with alcohol are not recommended. Clearly, there is a great unmet need for a new approach to prevent and/or treat mucositis.

Objective/Aim

Macrophages and gingival fibroblast cells are the major cells in mouth responding to mucositis. The goal of this study is to use an in vitro cell culture system of murine gingival cells (ESK‐1) to screen novel formulations of phosphatidycholine (PC) alone and PC‐complexed to the non‐steroidal anti‐inflammatory drug (NSAID), ibuprofen (IBU) for protection of the cells from clinically relevant challenges. The hypothesis is that PC, IBU and IBU‐PC will protect the gingival cells from injury due to cytotoxic agents such as, sodium dodecyl sulfate (SDS), lyso‐PC (LPC), and lipopolysaccharde (LPS), an endotoxin released by toxic bacteria due to the surface protective and/or anti‐inflammatory action of these agents.

Methods

The murine gingival ESK‐1 cells were cultured in the presence of injurious chemicals, cytotoxins and PC, IBU, or IBU‐PC was added at a range of doses. The damaging agents/toxins conditions included SDS ‐ a detergent commonly present in toothpaste, Lyso‐PC ‐ a metabolite of PC, and LPS ‐ an endotoxin released by toxic bacteria. The MTT assay was used to determine the number of cells protected and the LDH (lactate dehydrogenase) assay was used to test the cells damaged.

Results & Conclusion

The cell number, release of LDH, the cytosolic protein into the culture medium as indices of cytotoxicity, demonstrated that chemical‐induced injury to the gingival cells could be significantly reduced, if not prevented, by adding IBU‐PC or PC alone to the culture medium compared to IBU alone. Interestingly, LPS‐induced release of the pro‐inflammatory cytokine IL‐6 into the medium was significantly inhibited by IBU‐PC or IBU alone compared to PC alone, indicating the efficacy of IBU and IBU‐PC to block the release of this inflammatory mediator. Taken together, IBU‐PC could be an ideal drug in combined benefit of gingival cell protection and inhibiting inflammation of the oral mucosa. Supported by a NIH NCI grant, 1R21CA202751.

Support or Funding Information

Supported by a NIH NCI grant, 1R21CA202751