Research Information System
BIOLOGICAL TRACE ELEMENT RESEARCH, vol.202, no.7, pp.3204-3214, 2024 (SCI-Expanded)
Synaptosomes offer an intriguing ex vivo model system for investigating the molecular mechanisms of neurodegenerative
processes. Lipoxygenases significantly affect the course of neurodegenerative diseases. Homeostasis of trace elements such as
zinc is necessary for the continuity of brain functions. In this study, we purpose to determine whether LOXBlock-1, a 12/15
lipoxygenase inhibitor, and zinc sulfate (
ZnSO4) provide any biochemical protection during neurodegenerative damage in
synaptosomes induced by amyloid beta 1-42 (Aβ1-42). In this study, animals (30 Wistar Albino male rats 30) were divided
into 5 groups (6 animals in each group): Control, 10μM Aβ1-42, 10μM Aβ1-42+25mM LOXBlock-1, 10μM Aβ1-42+10μM
ZnSO4,
and 10μM Aβ1-42+25mM LOXBlock-1+10μM ZnSO4.
Synaptosomes were isolated from the rat cerebral cortex.
Following, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, malondialdehyde (MDA) levels, adenosine deaminase (ADA)
levels, reduced-glutathione (GSH) levels, neuronal nitric oxide synthase (nNOS) levels, acetylcholinesterase (AChE) activity,
catalase (CAT) activity, and 8-OHdG levels in synaptosomes were detected according to the ELISA method. ADA and
AChE expression and protein levels were analyzed. MDA, nNOS, AChE, and 8-OHdG levels in synaptosomes treated with
Aβ1-42 resulted in an increase, while there was a decrease in ADA, GSH, and CAT levels (p<0.001 vs. control). Conversely,
LOXBlock-1 and ZnSO4
treatments in synaptosomes treated with Aβ1-42 decreased MDA, nNOS, AChE, and 8-OHdG
levels, while ADA, GSH, and CAT levels increased. Moreover, the most effective improvement was seen in the co-treatment
group of LOXBlock-1 and ZnSO4.
Our data showed that LOXBlock-1 and ZnSO4
co-treatment may protect against Aβ1-42
exposure in rat brain synaptosomes.
Keywords Alzheimer’s diseases · LOXBlock-1 · Nitrosative stress · Oxidative stress · Synaptosome · Zinc sulfate