Enoxaparin prevents CXCL16/ADAM10-mediated cisplatin renal toxicity: Role of the coagulation system and the transcriptional factor NF-κB

C-X-C ligand 16 (CXCL16) is an exceptional chemokine that is expressed as transmembrane and soluble forms. Our aim is to shed lights on the role of CXCL16/ADAM10 (a disintegrin and metalloproteinase) in cisplatin (CP)-induced renal toxicity as well as possible protective effect of enoxaparin. Male a...

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Bibliographic Details
Published in:Life sciences (1973) 2021-04, Vol.270, p.119120, Article 119120
Main Authors: Aboyoussef, Amira M., Abdel-Sattar, Asmaa Ramadan, Abdel-Bakky, Mohamed Sadek, Messiha, Basim A.S.
Format: Article
Language:English
Subjects:
ADAM Proteins - metabolism
ADAM10
ADAM10 Protein - drug effects
ADAM10 Protein - metabolism
Amyloid Precursor Protein Secretases - metabolism
Animals
CD3
CD3 antigen
Cell Line, Tumor
Chemokine CXCL16 - drug effects
Chemokine CXCL16 - metabolism
Chemokines
Chemokines, CXC - metabolism
Cisplatin
Cisplatin - adverse effects
Cisplatin - pharmacology
Coagulation
CXCL16
CXCL16 protein
Enoxaparin
Enoxaparin - metabolism
Enoxaparin - pharmacology
Fibrin
Fibrinogen
Histopathology
Kidney - metabolism
Kidneys
Lymphocytes T
Male
Markers
Membrane Proteins - metabolism
Mice
NF-kappa B - metabolism
NF-κB protein
Parameters
Prothrombin
T-Lymphocytes - metabolism
Time dependence
Tissue factor
Tissues
Toxicity
Tubules
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Tumors
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Summary:C-X-C ligand 16 (CXCL16) is an exceptional chemokine that is expressed as transmembrane and soluble forms. Our aim is to shed lights on the role of CXCL16/ADAM10 (a disintegrin and metalloproteinase) in cisplatin (CP)-induced renal toxicity as well as possible protective effect of enoxaparin. Male albino mice were injected with CP (30 mg/kg, i.p.) in the presence or absence of enoxaparin (ENOX) (5 mg/kg, i.p.). Renal toxicity markers, serum level of cystatin-c, complete blood count (CBC), prothrombin time (Pt) and tissue expression of CXCL16, ADAM10, cluster of differentiation 3 (CD3), fibrinogen, tissue factor (TF), nuclear factor-κB (NF-κB) and tumour necrosis factor α (TNF-α) were measured. Besides, serum CXCL16 and histopathology were also analyzed. CP increased renal toxicity markers, renal expression of CXCL16/ADAM10, fibrinogen, TF and CD3 tissue expression in a time-dependent manner, and elevated serum cystatin-c, CXCL16 and tissue TNF-α, NF-κB. Alternatively, ENOX restored the deteriorated parameters and reduced tissue level of NF-κB. This report, for the first time, showed that soluble CXCL16 resulting from ADAM10 cleavage may recruit T-cells to the renal glomeruli and tubules in CP toxicity. Furthermore, TF and fibrin, have similar expression and location pattern like CXCL16 and ADAM10 suggesting their possible interrelation. ENOX successfully restored the deteriorated parameters suggesting it may be an effective nephroprotective adjuvant therapy.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2021.119120