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

Abstract

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. A chemoradiation-induced oral mucositis model was established by treating mice with concurrent 5-fluorouracil (100mg/kg, i.p.) and head and neck X-irradiation (20Gy). Phosphate-buffered saline or PLAG (100mg/kg or 250mg/kg, p.o.) was administered daily. Body weights were recorded daily, and mice were sacrificed on Day 9 for tongue tissue analysis. On Day 9, chemoradiotherapy-treated (ChemoRT) mice had tongue ulcerations and experienced significant weight loss (Day 0:26.18±1.41g; Day 9:19.44±3.26g). They also had elevated serum macrophage inhibitory protein 2 (MIP-2) (control: 5.57±3.49pg/ml; ChemoRT: 130.14±114.54pg/ml) and interleukin (IL)-6 (control: 198.25±16.91pg/ml; ChemoRT: 467.25±108.12pg/ml) levels. ChemoRT-treated mice who received PLAG exhibited no weight loss (Day 0:25.78±1.04g; Day 9:26.46±1.68g) and had lower serum MIP-2 (4.42±4.04pg/ml) and IL-6 (205.75±30.41pg/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. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol mitigated chemoradiation-induced oral mucositis by modulating necroptosis.