Nilotinib ameliorates folic acid-induced acute kidney injury through modulation of TWEAK and HSP-70 pathways

Purpose 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. Methods 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). Results 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. Conclusion 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.