1‐Palmitoyl‐2‐linoleoyl‐3‐acetyl‐rac‐glycerol ameliorates chemoradiation‐induced oral mucositis.

Objective: This study was designed to investigate whether necroptosis is involved in the pathogenesis of chemoradiation‐induced oral mucositis in a murine model and whether 1‐palmitoyl‐2‐linoleoyl‐3‐acetyl‐rac‐glycerol (PLAG) ameliorates this disorder. Materials and Methods: A chemoradiation‐induced oral mucositis model was established by treating mice with concurrent 5‐fluorouracil (100 mg/kg, i.p.) and head and neck X‐irradiation (20 Gy). Phosphate‐buffered saline or PLAG (100 mg/kg or 250 mg/kg, p.o.) was administered daily. Body weights were recorded daily, and mice were sacrificed on Day 9 for tongue tissue analysis. Results: On Day 9, chemoradiotherapy‐treated (ChemoRT) mice had tongue ulcerations and experienced significant weight loss (Day 0:26.18 ± 1.41 g; Day 9:19.44 ± 3.26 g). They also had elevated serum macrophage inhibitory protein 2 (MIP‐2) (control: 5.57 ± 3.49 pg/ml; ChemoRT: 130.14 ± 114.54 pg/ml) and interleukin (IL)‐6 (control: 198.25 ± 16.91 pg/ml; ChemoRT: 467.25 ± 108.12 pg/ml) levels. ChemoRT‐treated mice who received PLAG exhibited no weight loss (Day 0:25.78 ± 1.04 g; Day 9:26.46 ± 1.68 g) and had lower serum MIP‐2 (4.42 ± 4.04 pg/ml) and IL‐6 (205.75 ± 30.41 pg/ml) levels than ChemoRT‐treated mice who did not receive PLAG. Tongue tissues of mice who received PLAG also displayed lower phosphorylation levels of necroptotic signalling proteins. Conclusion: 1‐Palmitoyl‐2‐linoleoyl‐3‐acetyl‐rac‐glycerol mitigated chemoradiation‐induced oral mucositis by modulating necroptosis. [ABSTRACT FROM AUTHOR]