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

• Published in: Oral diseases 2020-01, Vol.26 (1), p.111-121
• Main Authors: Choi, Solji, Shin, Su‐Hyun, Lee, Ha‐Reum, Sohn, Ki‐Young, Yoon, Sun Young, Kim, Jae Wha
• Format: Article
• Language: English
• Subjects: 1‐palmitoyl‐2‐linoleoyl‐3‐acetyl‐rac‐glycerol (PLAG); 5-Fluorouracil; Animal models; Animals; Body weight loss; Chemokine CXCL2 - blood; chemoradiation‐induced oral mucositis; Chemoradiotherapy; Chemoradiotherapy - adverse effects; Chemotherapy; damage‐associated molecular pattern molecules (DAMPs); Dentistry; Diglycerides - pharmacology; Fluorouracil - adverse effects; Glycerol; Head and neck; Interleukin-6 - blood; Macrophages; Male; Mice; Mice, Inbred BALB C; Mucositis; Necroptosis; neutrophils; Phosphorylation; Radiation therapy; Rodents; Stomatitis - drug therapy; Stomatitis - etiology; Tongue
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.13224

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.