Involvement of MEF-2 and Apo-1/Fas in the Modulatory Mechanism of Liposomal Curcumin Against Cardiac Hypoxia

Background/Objectives: Hypoxia is a severe pathological complication associated with many disorders, as oxygen insufficiency could decline normal cellular homeostasis. Hypoxia causes alteration of the coronary blood flow and reduction of the contractile performance, which eventually leads to myocardial dysfunction. Thus, the current study aims to explore the potential cardioprotective effect of liposomal curcumin (L-CR) against sodium nitrite (NaNO2)-induced hypoxic stress. Methods: Hypoxia was induced by a single subcutaneous dose of NaNO2 (60 mg/kg), and a prophylactic intraperitoneal dose of either CR or L-CR was given two hours prior to NaNO2 intoxication. Oxidative stress, inflammatory and apoptotic responses in heart tissues were analyzed using molecular, histopathological and immunohistochemical techniques. Results: NaNO2 caused a significant increase in creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and C-reactive protein (CRP), as well as a decline in interleukin-10 (IL-10) levels. Additionally, the hypoxic heart exhibited a significant upregulation of cytochrome c and myocyte enhancer factor-2 (MEF-2), and downregulation of the nuclear factor erythroid-related factor 2 (Nrf-2). Moreover, NaNO2 induced cellular infiltration with a strong immunoreaction towards Apo-1/Fas, as displayed in the histopathological and immunohistochemical examinations. Using either CR or L-CR improved all the altered parameters. Conclusion: L-CR demonstrated a significant modulation in the expression of some parameters including CK-MB, MEF-2, Nrf-2, and Apo-1/Fas compared to native CR against cardiac stress induced by NaNO2.