Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.
Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madina Al-Munawwarah, 30001, Saudi Arabia. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.
Toxicology. 2019 Nov 1;427:152303. doi: 10.1016/j.tox.2019.152303. Epub 2019 Oct 5.
Acute Kidney Injury (AKI) is a global health concern associated with high morbidity and mortality. Experimental folic acid-induced AKI is comparable to human AKI and is repeatedly reported to study the pathogenic pathway of human AKI and study the therapeutic efficacy of different agents against AKI. In the present study, nilotinib has been investigated for its possible ameliorative potential against folic acid-induced AKI.
AKI was induced by IP injection of single dose (250 mg/kg) folic acid in mice. Nilotinib (15 mg/kg and 25 mg/kg) was administered orally by different treatment regimens (pre, post, and pre + post).
Folic acid injection induced marked AKI in mice. Nilotinib (25 mg/kg) successfully alleviated folic acid-induced AKI. Nilotinib significantly decreased folic acid-induced elevation in serum Cr, BUN, LDH and urine MTP, kidney MDA content and significantly increased folic acid-induced reduction in serum albumin, CrC, urine urea, kidney SOD activity and GSH content. Kidney TWEAK, IL-18, IL-1β, TNF-α, NF-κB, Caspase 3 and Bax contents significantly decreased upon nilotinib administration while, kidney contents of Bcl2 and HSP-70 significantly increased.
Anti-inflammatory, anti-apoptotic and anti-oxidant potentials are the main mechanisms by which nilotinib can ameliorate folic acid-induced AKI. Modulation of TWEAK and HSP 70 pathways are thought to be the main contributor to the observed ameliorative potential.
急性肾损伤（AKI）是一个全球性的健康问题，与高发病率和死亡率有关。实验性叶酸诱导的 AKI 与人类 AKI 相似，并且经常被用来研究人类 AKI 的发病机制，并研究不同药物对 AKI 的治疗效果。在本研究中，尼洛替尼被研究其对叶酸诱导的 AKI 的可能改善潜力。
通过单次腹腔注射叶酸（250mg/kg）诱导 AKI 模型。尼洛替尼（15mg/kg 和 25mg/kg）通过不同的治疗方案（预先、后和预先+后）进行口服给药。
叶酸注射诱导小鼠发生明显的 AKI。尼洛替尼（25mg/kg）成功缓解了叶酸诱导的 AKI。尼洛替尼显著降低了叶酸诱导的血清 Cr、BUN、LDH 和尿 MTP 升高，肾脏 MDA 含量，并显著增加了叶酸诱导的血清白蛋白、CrC、尿尿素、肾脏 SOD 活性和 GSH 含量的降低。尼洛替尼给药后，肾脏 TWEAK、IL-18、IL-1β、TNF-α、NF-κB、Caspase 3 和 Bax 含量显著降低，而肾脏 Bcl2 和 HSP-70 含量显著增加。
抗炎、抗凋亡和抗氧化潜力是尼洛替尼改善叶酸诱导的 AKI 的主要机制。TWEAK 和 HSP70 途径的调节被认为是观察到的改善潜力的主要贡献者。
