Protective effect of Lycopene/Lycopene cubosomal nanoparticles against cisplatin-induced cardiotoxicity: the function of NF-ҡB/HO-1 and Sirt1/AMPK/PGC1-α signaling pathways

Abstract

One antineoplastic agent with a wide variety of anticancer properties is Cisplatin (Cis). The strong antioxidant lycopene has garnered a lot of interest from researchers due to its possible health advantages. The purpose of this work was to determine probable mechanisms behind the cardioprotective benefits and explore the innovative application of Lycopene Nanoformulation to reduce Cis-induced cardiotoxicity. Lycopene-Cub-NPs were characterized using particle size, zeta potential, PDI, SEM, TEM, and FTIR. Rats were allocated into seven groups: (1) Control, (2) Control polymer, (3) Lycopene Free, (4) Lycopene-Cub-NPs, (5) Cis, (6) Lycopene Free + Cis, and (7) Lycopene-Cub-NPs + Cis, with Cis (10 mg/kg, I.P.) administered once on day 27 to groups 5–7. The oxidative stress markers MDA, CAT, SOD, GSH, GPX-1, and GST in heart tissue were measured using ELISA. The content of PGC1-α, AMPK, IL-10, HO-1, Cytochrome c, Caspase 9, and BAX was also measured using ELISA. The relative gene expression of Sirt1, AMPK, PGC1-α, NF-ҡB, IL-10, HO-1, Caspase 3, and Bcl-2 was evaluated by qRT-PCR using β-actin as a housekeeping gene. Cis dramatically raised the activity of the heart damage markers CK-MB and LDH. Catalase and superoxide dismutase activities were reduced, while myocardial MDA content rose as well. Similarly, Cis exhibits a notable downregulation in Sirt1, AMPK, PGC1-α, IL-10, HO-1, and Bcl-2, and an elevation in the NF-ҡB, Cytochrome c, Caspase 9, BAX, and Caspase 3 gene and protein expression. Pretreatment with Lycopene-Cub-NPs demonstrated the strongest recovery of the altered histological, immunohistochemical, and biochemical features as compared to Lycopene Free. This study demonstrated that Lycopene-Cub-NPs mitigate Cis-induced cardiotoxicity in vivo, likely through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting their potential as a novel cardioprotective strategy.