Evaluating the protective role of trimetazidine versus nano-trimetazidine in amelioration of bilateral renal ischemia/reperfusion induced neuro-degeneration: Implications of ERK1/2, JNK and Galectin-3 /NF-κB/TNF-α/HMGB-1 signaling

• Published in: Tissue & cell Vol. 85; p. 102241
• Main Authors: Hassan, Fatma E., Aboulhoda, Basma Emad, Ali, Isra H., Elwi, Heba M., Matter, Lamiaa M., Abdallah, Hend Ahmed, Khalifa, Mohamed Mansour, Selmy, Asmaa, Alghamdi, Mansour A., Morsy, Suzan Awad, Al Dreny, Basant A.
• Format: Journal Article
• Language: English
• Published: 01.12.2023
• ISSN: 0040-8166; 1532-3072
• DOI: 10.1016/j.tice.2023.102241

BACKGROUNDRenal ischemia/reperfusion (I/R) is a primary culprit of acute kidney injury. Neurodegeneration can result from I/R, but the mechanisms are still challenging. We studied the implications of bilateral renal I/R on brain and potential involvement of the oxidative stress (OS) driven extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase (ERK1/2, JNK) and Galectin-3 (Gal-3)/nuclear factor Kappa B (NF-қB)/tumor necrosis factor-alpha (TNF-α), high mobility group box-1 (HMGB-1), and caspase-3 paths upregulation. We tested the impact of Nano-trimetazidine (Nano-TMZ) on these pathways being a target of its neuroprotective effects.METHODSStudy groups; Sham, I/R, TMZ+I/R, and Nano-TMZ+I/R. Kidney functions, cognition, hippocampal OS markers, Gal-3, NF-қB, p65 and HMGB-1 gene expression, TNF-α level, t-JNK/p-JNK and t-ERK/p-ERK proteins, caspase-3, glial fibrillary acidic protein (GFAP) and ionized calcium binding protein-1 (Iba-1) were assessed.RESULTSNano-TMZ averted renal I/R-induced hippocampal impairment by virtue of its anti: oxidative, inflammatory, and apoptotic properties.CONCLUSIONNano-TMZ is more than anti-ischemic.