Hepatoprotective effect of the tyrosine kinase inhibitor nilotinib against cyclosporine-A induced liver injury in rats through blocking the Bax/Cytochrome C/caspase-3 apoptotic signaling pathway.

摘要: Cyclosporine-A (CsA) is a powerful immunosuppressive agent and hepatotoxicity results from CsA treatment. This study aimed to elucidate the effectiveness of tyrosine kinase inhibitor nilotinib against CsA-induced underlying molecular mechanisms. Male Sprague-Dawley rats were allocated into four groups received drugs for 28 days as follows: Control group: vehicle, Nilotinib (20 mg/kg orally), by subcutaneous injection daily), CsA-nilotinib: CsA. Serum lactate dehydrogenase (LDH), liver function biomarkers, hepatic levels oxidative stress nuclear factor erythroid-2 like-2 (Nrf2), total antioxidant capacity (TAC), interleukin-2 (IL-2), IL-1β, IL-6, cytochrome-C assessed. Additionally, protein mRNA expression Bcl2 associated X (Bax), caspase-3, factor-κB (NF-κB), hemoxygenase-1 (HO-1) measured. Moreover, tissues assessed histopathologically using hematoxylin-eosin Masson trichrome stain. treatment decreased serum LDH, alanine aminotransferase, aspartate γ-glutamyltransferase (γ-GT), malondialdehyde, cytochrome-C. It also increased superoxide dismutase, reduced glutathione, glutathione reductase, peroxidase, glutathione-S-transferase (GST), TAC, Nrf2 compared CsA-injected rats. In addition, NF-κB, Bax, while elevated IL-2 immunoexpression HO-1. Bax caspase-3 was that HO-1 inhibitory κB-α in nilotinib-treated group. significantly attenuated histopathological alterations. may have promising role hepato-protective through its antiapoptotic, antioxidant, anti-inflammatory effects.