Sphingosine-1-phosphate alleviates irradiation-induced parotid injury in a miniature pig model

Oral Dis. 2020 Jul;26(5):920-929. doi: 10.1111/odi.13302. Epub 2020 Mar 10.

Abstract

Objectives: Our aim was to verify the alleviation effect of sphingosine-1-phosphate (S1P) in a miniature pig model.

Material and methods: Thirty male miniature pigs were randomly separated into 10 groups in our experiment. We administered S1P through the parotid duct in a retrograde fashion 2 hr before irradiation (IR). The salivary flow rate and blood flow rate were tested 20 weeks after IR. The apoptotic level was checked at 12, 24 hr and 7 days post-IR.

Results: Twenty weeks after IR, the salivary flow rate of the IR-side parotid gland in IR + S1P group can be maintained at about 40% of the non-IR side, while only 20% was maintained in the IR group. The blood flow rate and microvascular density were significantly higher in the IR + S1P group than in the IR group. The apoptotic level and cleaved caspase-3 expression were downregulated in IR + S1P group, and the ratio of Bcl-2/Bax was increased. The blood flow rate and CD31 level were significantly restored at 12, 24 hr and 7 days post-IR.

Conclusion: Sphingosine-1-phosphate may partially alleviate IR-induced parotid dysfunction by decreasing apoptosis of microvascular endothelial cells and maintaining the blood flow rate.

Keywords: apoptosis; hyposalivation; pig model; radiotherapy; sphingosine-1-phosphate.

MeSH terms

  • Animals
  • Apoptosis
  • Endothelial Cells*
  • Lysophospholipids* / pharmacology
  • Male
  • Parotid Gland* / radiation effects
  • Radiation Injuries* / drug therapy
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Swine
  • Swine, Miniature

Substances

  • Lysophospholipids
  • sphingosine 1-phosphate
  • Sphingosine