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

Fatma E Hassan; Basma Emad Aboulhoda; Isra H Ali; Heba M Elwi; Lamiaa M Matter; Hend Ahmed Abdallah; Mohamed Mansour Khalifa; Asmaa Selmy; Mansour A Alghamdi; Suzan Awad Morsy; Basant A Al Dreny

doi:10.1016/j.tice.2023.102241

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

Tissue Cell. 2023 Dec:85:102241. doi: 10.1016/j.tice.2023.102241. Epub 2023 Oct 16.

Authors

Affiliations

¹ Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University, Giza 11562, Egypt; General Medicine Practice Program, Department of Physiology, Batterjee Medical College, Jeddah 21442, Saudi Arabia.
² Anatomy and Embryology Department, Faculty of Medicine, Cairo University, Egypt. Electronic address: Basma.emad@kasralainy.edu.eg.
³ Department of Pharmaceutics, Faculty of Pharmacy, University of Sadat City, P.O. Box 32897, Sadat City, Egypt; Nanomedicine Laboratory, Faculty of Pharmacy, University of Sadat City, P.O. Box 32897, Sadat City, Egypt.
⁴ Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Egypt.
⁵ Medical pharmacology, Kasr Alainy, Faculty of Medicine, Cairo University, Egypt.
⁶ Anatomy and Embryology Department, Faculty of Medicine, Cairo University, Egypt.
⁷ Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University, Giza 11562, Egypt; Department of Human Physiology, College of Medicine, King Saud University, Saudi Arabia.
⁸ Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University, Giza 11562, Egypt.
⁹ Department of Anatomy, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia; Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia.
¹⁰ Fakeeh College For Medical Sciences, Jeddah, Saudi Arabia; Faculty of Medicine, Alexandria University, Egypt.

PMID: 37865040
DOI: 10.1016/j.tice.2023.102241

Abstract

Background: Renal 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.

Methods: Study 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.

Results: Nano-TMZ averted renal I/R-induced hippocampal impairment by virtue of its anti: oxidative, inflammatory, and apoptotic properties.

Conclusion: Nano-TMZ is more than anti-ischemic.

Keywords: Brain; Galectin-3, HMGB-1; Nano-Trimetazidine; Oxidative stress.

MeSH terms

Caspase 3 / metabolism
Galectin 3 / metabolism
HMGB Proteins / metabolism
Humans
Ischemia
Kidney Diseases*
MAP Kinase Signaling System
NF-kappa B / metabolism
Reperfusion
Reperfusion Injury* / metabolism
Trimetazidine* / pharmacology
Tumor Necrosis Factor-alpha / metabolism

Substances

Trimetazidine
NF-kappa B
Tumor Necrosis Factor-alpha
Galectin 3
Caspase 3
HMGB Proteins