Fucoxanthin alters the apelin-13/APJ pathway in certain organs of γ-irradiated mice

J Radiat Res. 2021 Jul 10;62(4):600-617. doi: 10.1093/jrr/rraa141.

Abstract

Apelin-13 and APJ are implicated in different key physiological processes. This work aims at exploring the radioprotective effect of fucoxanthin (FX) on γ-radiation (RAD)-induced changes in the apelin-13/APJ pathway, which causes damage in the liver, kidney, lung and spleen of mice. Mice were administered FX (10 mg kg-1 day-1, i.p) and exposed to γ-radiation (2.5 Gy week-1) for four consecutive weeks. The treatment of irradiated mice by FX resulted in a significant amendment in protein expression of the apelin-13/APJ/NF-κB signalling pathway concurrently with reduced hypoxia (hypoxia-inducible factor-1α), suppressed oxidative stress marker (malondialdehyde), enhanced antioxidant defence mechanisms (reduced glutathione and glutathione peroxidase), a modulated inflammatory response [interleukin-6 (IL-6), monocyte chemoattractant protein-1, IL-10 and α-7-nicotinic acetylcholine receptor) and ameliorated angiogenic regulators [matrix metalloproteinase (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1), as well as the tissue damage indicator (lactate dehydrogenase) in organ tissues. In addition, there were significant improvement in serum inflammatory markers tumour necrosis factor-α, IL-10, IL-1β and C-reactive protein compared with irradiated mice. The histopathological investigation of the FX + RAD organ tissues support the biochemical findings where the improvements in the tissues' architecture were obvious when compared with those of RAD. FX was thus shown to have a noticeable radioprotective action mediated through its regulatory effect on the apelin-13/APJ/NF-κB signalling pathway attributed to its antioxidant and anti-inflammatory activity that was reflected in different physiological processes. It could be recommended to use FX in cases of radiation exposure to protect normal tissues.

Keywords: Apelin-13/APJ; Fucoxanthin; MMP-9; α-7nAchR; γ-radiation.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apelin Receptors / metabolism
  • Gamma Rays
  • Inflammation / pathology
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / radiation effects
  • L-Lactate Dehydrogenase / metabolism
  • Liver / drug effects
  • Liver / pathology
  • Liver / radiation effects
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Organ Specificity / drug effects
  • Organ Specificity / radiation effects*
  • Oxidants / metabolism
  • Signal Transduction* / drug effects
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Whole-Body Irradiation*
  • Xanthophylls / pharmacology*

Substances

  • Antioxidants
  • Apelin Receptors
  • Intercellular Signaling Peptides and Proteins
  • NF-kappa B
  • Oxidants
  • Tissue Inhibitor of Metalloproteinase-1
  • Xanthophylls
  • apelin-13 peptide
  • fucoxanthin
  • L-Lactate Dehydrogenase
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9