Neurochemical Research of LOXBlock-1 and ZnSO against Neurodegenerative Damage Induced by Amyloid Beta(1-42).

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 (ZnSO) 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 ZnSO, and 10µM Aβ1-42+25mM LOXBlock-1+10µM ZnSO. 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 ZnSO 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 ZnSO. Our data showed that LOXBlock-1 and ZnSO co-treatment may protect against Aβ1-42 exposure in rat brain synaptosomes.