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-1ß 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.
Subject(s)
Intercellular Signaling Peptides and Proteins/metabolism , Organ Specificity/radiation effects , Signal Transduction , Whole-Body Irradiation , Xanthophylls/pharmacology , Animals , Antioxidants/metabolism , Apelin Receptors/metabolism , Gamma Rays , Inflammation/pathology , 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 , Oxidants/metabolism , Signal Transduction/drug effects , Tissue Inhibitor of Metalloproteinase-1/metabolismABSTRACT
BACKGROUND: Cancer remains a major health issue and the second foremost root of morbidity worldwide behind cardiovascular diseases. Apoptosis had linked to the eradication of possibly malignant cells, hyperplasia, and tumor progression. OBJECTIVE: The present study is an endeavor to evaluate the influence of luteolin, a modifier to apoptotic regulator on the tumor growth and the tumor cell sensitivity to ionizing radiation in Ehrlich solid tumor-bearing mice (E). MATERIALS AND METHODS: Mice were immunized with Ehrlich carcinoma cells (2.5 × 106 cells/mouse), received consecutive equal doses of luteolin, 1.25 mg/mouse/day and exposed to 6.5 Gy of whole-body gamma irradiation (0.46 Gy/min). RESULTS: Luteolin markedly suppresses the developing of tumor in E mice group or mice which bearing tumor with exposure to radiation (E + R group) which has collimated with significant inhibition in protein expression of inflammatory molecules cyclooxygenase 2 and the concentration of (prostaglandin E2). Also, matrix metalloproteinase-2, 9 proteins concentrations significantly decreased with amelioration in apoptotic regulators (Caspase-3 and Granzyme-B activities). The expression of signal transducer and activator of transcription (STAT) and tumor necrosis factor-alpha genes meliorated significantly. Besides, the level of oxidant/antioxidant (reduced glutathione/malondialdehyde) markedly improved. Obviously, the most reduction of changes in all measured parameters has appeared in tumor bearing mice, injected with luteolin and exposed to gamma radiation (E + Luteolin + R group). CONCLUSION: It could be suggested that luteolin has a potential beneficial effect against cancer. This could be due to its ability on the induction of apoptosis, inhibition of inflammatory response, downregulation of angiogenic factors as well as increase sensitivity of tumor cells to gamma radiation.