الفهرس 
Introduction & Aim of the workOnly 14 pages are availabe for public view
 |  | from | 194 |  |  |
| | | from | 194 | | |
Abstract
Background: Cyclosporin A (CsA) is an immunosuppressive agent that can be used for the remedy of autoimmune diseases. Despite its hepatotoxicity, CsA is still a backbone in organ transplantation. Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was approved by FDA for its anthelmintic properties. Niclosamide (NCL) is oral anthelmintic medication used to treat most tapeworm infections for around 50 years.
Aim:The current study was conducted to assess the conceivable protective effects of PP and NCL against CSA induced hepatotoxicity and the possible underlying mechanisms for these effects.
Method:100 male albino mice were divided into ten groups each experiment contains 5 group; group 1 in both experiment is considered as a control group, while group 2 is considered as a CsA group, groups 3 and 4 in both experiments were subjected to daily CsA (25 mg/kg, i.p) and treated with graded dose of NCL (2.5, 5mg/kg, i.p) in experiment 1 and PP (0.25, 0.5mg/kg, i.p) in experiment 2. Finally, group 5 was treated with NCL (5 mg/ kg, i.p) in experiment 1 and PP (0.5 mg/ kg, i.p) in experiment 2 for 21 days. Mice were sacrificed under anesthesia, then livers were removed for histopathological and biochemical investigations.
Results:CsA caused a significant increase in the liver enzymes, total bilirubin and malondialdehyde (MDA). In contrast, the levels of albumin, glutathione and the antioxidants enzymes were significantly decreased in CsA-treated group. Furthermore, the tissue levels of tumor necrosis factor-alpha (TNF-α), interleukine-1β (IL-1β) and nuclear factor kappa-β NF-κB) were significantly increased with CsA treatment. Along with, significant rise in P53 expression. CsA activated Wnt/β-catenin signaling by increasing the expression of Wnt3a, frizzled receptor-7, β-catenin and c-myc. On the other hand, the levels of PPAR-γ decreased significantly with CsA. PP and NCL significantly attenuated CsA-evoked alterations in the previous-stated parameters highlighting their antioxidant, anti-inflammatory and anti-apoptotic potential.
Conclusions:PP and NCL may be considered as promising agents to prevent CsA hepatotoxicity.