الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Renal fibrosis is a progressive process resulting from sustained injury that may ultimately cause renal failure. Cisplatin is an antitumour drug that induces renal injury and nephrotoxicity and is widely employed as a model for acute and chronic renal injury. Several signaling pathways are implicated in fibrogenic cell activation among which is Hedgehog (Hh) signaling. We here investigated the effects of arsenic trioxide (Ars) and curcumin in ameliorating cisplatin-induced kidney fibrosis via regulating Hh signaling. Cisplatin (4.5 mg/kg) was administered in Sprague Dawley rats for two consecutive days and renal fibrosis was induced after 21 days. Once renal fibrosis was confirmed, Ars (3.5 mg/kg /day, orally) and curcumin (200 mg/kg /day, orally) were administered daily for another 21 days. Ars and curcumin corrected kidney function markers as creatinine clearance and urea nitrogen. Both agents ameliorated fibrosis as shown by lowered TGF-β1 mRNA levels, α-SMA protein levels and hydroxylproline content. Cisplatin activated Hh signaling which was blocked by both Ars and curcumin as demonstrated by decreased mRNA levels of Shh, Smo and Ptch and suppressed renal Gli1 and Gli2 protein levels. Our results indicate new therapeutic roles for Ars and curcumin and suggest that blocking Hh signaling may be a promising approach for alleviating renal fibrosis. Arsenic trioxide, curcumin, and their combination significantly improved kidney function, oxidative stress, fibrosis marker, Hh pathway expression and kidney fibrosis scores and kidney tubular injury in kidney injury and kidney fibrosis. In conclusion, this study demonstrated that Hh pathway is developmental signalling pathway that is strongly up-regulated in renal fibrosis. Arsenic trioxide and Curcumin can inhibit changes in fibrosis induced experimentally in rats, possibly by down regulate of the Hh pathway. The ability of Arsenic trioxide and Curcumin to target various pathways involved in fibrosis make it a promising therapy for the management of kidney fibrosis.