Pharmacology and Toxicology Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; Pharmacology and Toxicology Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt.
Life Sci. 2021 Apr 1;270:119120. doi: 10.1016/j.lfs.2021.119120. Epub 2021 Feb 2.
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.
C-X-C 趋化因子配体 16（CXCL16）是一种特殊的趋化因子，可表达为跨膜和可溶性形式。我们的目的是阐明 CXCL16/ADAM10（解整合素和金属蛋白酶）在顺铂（CP）诱导的肾毒性中的作用以及依诺肝素的可能保护作用。
雄性白化小鼠腹腔注射 CP（30mg/kg），并在存在或不存在依诺肝素（ENOX）（5mg/kg，腹腔注射）的情况下进行注射。测量肾毒性标志物、血清胱抑素 C 水平、全血细胞计数（CBC）、凝血酶原时间（Pt）以及 CXCL16、ADAM10、分化群 3（CD3）、纤维蛋白原、组织因子（TF）、核因子-κB（NF-κB）和肿瘤坏死因子-α（TNF-α）的组织表达。此外，还分析了血清 CXCL16 和组织病理学。
CP 呈时间依赖性增加肾毒性标志物、肾脏 CXCL16/ADAM10、纤维蛋白原、TF 和 CD3 组织表达，并升高血清胱抑素 C、CXCL16 和组织 TNF-α、NF-κB。相反，ENOX 恢复了恶化的参数并降低了组织 NF-κB 水平。
本报告首次表明，ADAM10 切割产生的可溶性 CXCL16 可能在 CP 毒性中招募 T 细胞到肾小球和肾小管。此外，TF 和纤维蛋白与 CXCL16 和 ADAM10 具有相似的表达和位置模式，表明它们可能存在相互关系。ENOX 成功恢复了恶化的参数，表明它可能是一种有效的肾保护辅助治疗方法。
