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

Abstract

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.

• Authors: Solji Choi, Su-Hyun Shin, Ha-Reum Lee, Ki-Young Sohn, Sun Young Yoon, Jae Wha Kim
• Journal: Oral diseases (Oral Dis) Vol. 26 Issue 1 Pg. 111-121 (Jan 2020) ISSN: 1601-0825 [Electronic] Denmark
• PMID: 31677207 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Oral Diseases published by John Wiley & Sons Ltd.

Chemical References

• 1-palmitoyl-2-linoleoyl-3-acetyl-rac glycerol
• Chemokine CXCL2
• Cxcl2 protein, mouse
• Diglycerides
• Interleukin-6
• interleukin-6, mouse
• Fluorouracil

Topics

• Animals
• Chemokine CXCL2 (blood)
• Chemoradiotherapy (adverse effects)
• Diglycerides (pharmacology)
• Fluorouracil (adverse effects)
• Interleukin-6 (blood)
• Male
• Mice
• Mice, Inbred BALB C
• Stomatitis (drug therapy, etiology)