Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Renal ischemia-reperfusion injury (I/RI) remains a critical clinical situation. Several evidence revealed the potential reno-protective effects of Vitamin D and/or pioglitazone, on renal I/RI. This study addresses the possible involvement of the Wnt4/Ý-catenin signaling, p-S536NF-mBp65, PPARÞ, Ang II/TGF-Ý, and ACE2 as potential effectors to vitamin D and pioglitazone-mediated renoprotective effects . Two sets of Sprague-Dawley rats (n=30 rat each), were randomized into sham, I/R, Vit D "alfacalcidol" (5 ng/kg/day), pioglitazone (5 mg/kg/day), and Vit D + pioglitazone groups. In all groups renal biochemical parameters, as well as inflammatory and structural profiles were assessed, besides the expression/contents of Wnt4/Ý-catenin and pS536-NF-mBp65. All treatments started 7 days before I/RI and animals were killed 24 h after I/RI in the first set, while those in the 2nd set continued their treatments for 14 days. After 24 h, all pre-treatments impeded theI/R effect on neutrophils recruitment, p-S536NF-mBp65, IL-18, NGAL, caspase-3, AngII, ACE-2, PPARÞ and TGF-Ý, besides the expression of Wnt4 and ACE-2 with notable reflection on histological changes. Two weeks after I/RI, except a marked up regulation in Wnt4 expression and a striking elevation in the Ý-catenin content, the magnitude of the injurious events was relatively less pronounced, an effect that was mostly augmented by the different treatments. The current study pledges a promising and novel reno-protective role of the administration of Vit D and pioglitazone entailing a potential involvement of ICAM-1, MPO, NF-mB, Ang II, ACE2, TGFÝ, and a modulation of Wnt4/Ý-catenin pathway

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