Neurochemical Research of LOXBlock‑1 and ZnSO4 against Neurodegenerative Damage Induced by Amyloid Beta(1‑42)

Synaptosomes offer an intriguing ex vivo model system for investigating the molecular mechanisms of neurodegenerativeprocesses. Lipoxygenases significantly affect the course of neurodegenerative diseases. Homeostasis of trace elements such aszinc is necessary for the continuity of brain functions. In this study, we purpose to determine whether LOXBlock-1, a 12/15lipoxygenase inhibitor, and zinc sulfate (ZnSO4) provide any biochemical protection during neurodegenerative damage insynaptosomes induced by amyloid beta 1-42 (Aβ1-42). In this study, animals (30 Wistar Albino male rats 30) were dividedinto 5 groups (6 animals in each group): Control, 10μM Aβ1-42, 10μM Aβ1-42+25mM LOXBlock-1, 10μM Aβ1-42+10μMZnSO4,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 andAChE expression and protein levels were analyzed. MDA, nNOS, AChE, and 8-OHdG levels in synaptosomes treated withAβ1-42 resulted in an increase, while there was a decrease in ADA, GSH, and CAT levels (p&lt;0.001 vs. control). Conversely,LOXBlock-1 and ZnSO4treatments in synaptosomes treated with Aβ1-42 decreased MDA, nNOS, AChE, and 8-OHdGlevels, while ADA, GSH, and CAT levels increased. Moreover, the most effective improvement was seen in the co-treatmentgroup of LOXBlock-1 and ZnSO4.Our data showed that LOXBlock-1 and ZnSO4co-treatment may protect against Aβ1-42exposure in rat brain synaptosomes.Keywords Alzheimer’s diseases · LOXBlock-1 · Nitrosative stress · Oxidative stress · Synaptosome · Zinc sulfate</p

Capsaicin induces redox imbalance and ferroptosis through ACSL4/ GPx4 signaling pathways in U87‑MG and U251 glioblastoma cells

Glioblastoma is one of the deadliest malignant gliomas. Capsaicin is a homovanillic acid derivative that can show anticancer efects by regulating various signaling pathways. The aim of this study is to investigate the efects of capsaicin oncell proliferation via ferroptosis in human U87-MG and U251 glioblastoma cells. Firstly, efects of capsaicin treatment oncell viability were determined by MTT analysis. Next, cellular-proliferation and cytotoxicity assays were determined byanalyzing bromodeoxyuridine (BrdU) and lactate dehydrogenase (LDH) activity, respectively. Following, acyl-CoA synthetase long chain family member 4 (ACSL4), glutathione peroxidase 4 (GPx4), 5-hydroxyeicosatetraenoic acid (5-HETE),total oxidant status (TOS), malondialdehyde (MDA), total antioxidant status (TAS) and reduced glutathione (GSH) levelswere determined by ELISA. Additionally, ACSL4 and GPx4 mRNA and protein levels were analyzed. Capsaicin showed aconcentration-dependent anti-proliferative efects in U87-MG and U251 cells. Cell viability was decreased in the both celllines treated with capsaicin concentrations above 50&nbsp;μM, while LDH activity increased. Treatment of 121.6, 188.5, and237.2&nbsp;μM capsaicin concentrations for 24&nbsp;h indicated an increase in ACSL4, 5-HETE, TOS and MDA levels in U87-MG andU251 cells (p&lt;0.05). On the other hand, we found that capsaicin administration caused a decrease in BrdU, GPx4, TAS andGSH levels in U87-MG and U251 cells (p&lt;0.05). Besides, ACSL4 mRNA and protein levels were increased in the glioblastoma cells treated with capsaicin, whereas GPx4 mRNA and protein levels were decreased. Finally, capsaicin might be usedas a potential anticancer agent with ferroptosis-induced anti-proliferative efects in the treatment of human glioblastoma.</p

Anti-oxidative and apoptotic properties of curcumin as a mechanism of its antineoplastic potential in U251 cells

Glioblastoma is the most aggressive of all types of brain cancer. Especially in cancer research, the effectiveness of new drug candidates is being investigated with in vitro studies. In this study, we aimed to investigate the antineoplastic effects of curcumin administration at different doses on U251 cells. We hypothesize that curcumin inhibits U251 cell viability by modulating prooxidant-antioxidant mechanisms, triggering ROS production, apoptosis activity, and inflammation. In this study, IL-1β, TNF-α, caspase 3/9 levels, total antioxidant (TAS) and total oxidant levels (TOS) were measured. Cell viability was determined by MTT and 10, 20 and 40 µM curcumin doses were found to be effective doses. It was found that the administration of 40 µM curcumin induced oxidative stress, inflammation and apoptosis compared to the control group and other dose groups (p&lt;0.05). No statistical difference was found in the 10 µM curcumin group. We found that 40 µM curcumin had a dose-dependent effect on proliferation and migration of U251 glioblastoma cells and significantly inhibited their proliferation.</p