@article {207768,
	title = {Nicorandil prevents the nephrotoxic effect of cyclosporine-A in albino rats through modulation of HIF-1α/VEGF/eNOS signaling.},
	journal = {Canadian journal of physiology and pharmacology},
	volume = {99},
	year = {2021},
	pages = {411-417},
	abstract = {<p>Despite that cyclosporine-A (CsA) is a widely used immunosuppressive drug, its nephrotoxic effect limits its long-term administration. Herein we tried to investigate its renal effect on endothelial dysfunction targeting the hypoxia-inducible factor (HIF-1α)~/ vascular endothelial growth factor (VEGF)~/ endothelial nitric oxide synthase (eNOS) pathway and the possible modulation by nicorandil. Eight groups of adult male Wistar rats were included: (1) control; (2) vehicle group (received oil); (3) glibenclamide 5~mg{\textperiodcentered}kg{\textperiodcentered}day administered orally; (4) nicorandil 10~mg{\textperiodcentered}kg{\textperiodcentered}day administered orally; (5) CsA 25~mg{\textperiodcentered}kg{\textperiodcentered}day administered orally; (6) combined administration of CsA and nicorandil; (7) glibenclamide was added to CsA; and (8) both CsA and nicorandil were combined with glibenclamide. The treatment continued for six~weeks. Combined nicorandil with CsA improved renal function deterioration initiated by CsA. CsA decreased the renal expression levels (~\&lt; 0.001) of HIF-1α, eNOS, and VEGF, inducing endothelial dysfunction and triggering inflammation, and upregulated the profibrotic marker transforming growth factor (TGF-β). Nicorandil fixed the disturbed HIF-1α/VEGF/eNOS signaling. Nicorandil corrected the renal functions, confirmed by the improved histological glomerular tuft retraction that was obvious in the CsA group, without significant influence by glibenclamide. Proper protection from CsA-induced nephrotoxicity was achieved by nicorandil. Nicorandil reversed the disturbed HIF-1α/VEGF/eNOS pathway created by CsA.</p>
},
	author = {Harb, Inas A and Ashour, Hend and Dina Sabry and El-Yasergy, Dina Fawzy and Hamza, Wael Mostafa and Abeer Mostafa}
}
