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Alzheimer's disease (AD) is a progressive neurological disorder that affects various cognitive functions, behavior, and personality. AD is thought to be caused by a combination of genetic and environmental factors, including exposure to aluminum (Al). Virgin coconut oil (VCO) may have potential as a natural neuroprotectant against AD. Aim of this study was to determine neuroprotective effects of VCO on Al-induced neurotoxicity in an in vitro AD model. SH-SY5Y cells were initially cultured in normal growth medium and then differentiated by reducing fetal bovine serum content and adding retinoic acid (RA). Later, brain-derived neurotrophic factor (BDNF) was added along with RA. The differentiation process was completed on the seventh day. Study groups (n = 3) were designed as control group, VCO group, Al group, Al-VCO group, Alzheimer model (AD) group, AD + Al-exposed group (AD+Al), AD + VCO applied group (AD + VCO) and AD + Al-exposed + VCO applied group (AD + Al + VCO). Specific markers of AD (hyperphosphorylated Tau protein, amyloid beta 1-40 peptide, and amyloid precursor protein) were measured in all groups. In addition, oxidative stress parameters (total antioxidant capacity, lipid peroxidase, protein carbonyl, and reactive oxygen species) and neurotransmitter-related parameters (dopamine, dopamine transporter acetylcholine, and synuclein alpha levels, acetylcholinesterase activity) were measured comparatively in the study groups. VCO reduced amyloid beta and hyperphosphorylated Tau protein levels in the study groups. In addition, oxidative stress levels decreased, and neurotransmitter parameters improved with VCO. Our study shows that VCO may have potential therapeutic effects in Alzheimer's disease and further experiments are needed to determine its efficacy., (© 2023 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

Dihydrolipoic acid (DHLA) is a natural antioxidant known for its ability to counteract metal toxicity and oxidative stress. It has shown the potential to safeguard cells from harmful environmental substances. It may hold therapeutic benefits in treating neurodegenerative disorders by defending against oxidative damage and chronic inflammation. Thus, this study aimed to explore the potential neuroprotective effects of DHLA against aluminum (Al)-induced toxicity using an Alzheimer's disease (AD) model in vitro. The study focused on two important pathways: GSK-3β and the Wnt signaling pathways. The SH-SY5Y cell line was differentiated to establish AD, and the study group were as follows: control, Al, DHLA, Al-DHLA, AD, AD-Al, AD-DHLA, and AD-Al-DHLA. The impact of DHLA on parameters related to oxidative stress was assessed. The activity of the GSK-3β pathway was measured by evaluating the levels of PPP1CA, PP2A, GSK-3β, and Akt. The Wnt signaling pathway was assessed by measuring Wnt/β-catenin in the different study groups. Exposure to DHLA significantly reduced oxidative stress by effectively decreasing the levels of reactive oxygen species, thereby protecting against protein oxidation and limiting the production of malonaldehyde. Moreover, the DHLA-treated groups exhibited a remarkable increase in the total antioxidant capacity. Furthermore, the study observed an upregulation of the Wnt signaling pathway and a downregulation of the GSK-3β pathway in the groups treated with DHLA. In summary, the neuroprotective effects of DHLA, primarily achieved by reducing oxidative stress and modulating critical imbalanced pathways associated with AD, indicate its potential as a promising addition to the treatment regimens of AD patients., (© 2023 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

Short-chained alkyl mercury compounds accumulate in particularly in the brain. Exposure to these compounds is associated with various neurotoxic effects. Gender-based differences are observed in neurodevelopmental disorders, and testosterone and estradiol may alter the toxic effect of the compounds. The present study aimed to investigate the toxic effects of methylmercury and thimerosal on SH-SY5Y cells in high testosterone/low estradiol and high estradiol/low testosterone containing cellular environment and estimate whether male and female brains react differently to the toxic effects of methylmercury and thimerosal. Study groups (n = 3) were designed as control: growth medium, thimerosal (T): 1.15-μM thimerosal, methylmercury (M): 2.93-μM methylmercury, high testosterone/low estradiol + thimerosal (TT): 1-μM testosterone + 0.75-μM estradiol + 1.15-μM thimerosal, high estradiol/low testosterone + thimerosal (ET): 0.1-μM testosterone + 7.5-μM estradiol + 1.15-μM thimerosal, high testosterone/low estradiol + methylmercury (TM): 1-μM testosterone + 0.75-μM estradiol + 2.93-μM methylmercury and high estradiol/low testosterone + methylmercury (EM): 0.1-μM testosterone + 7.5-μM estradiol + 2.93-μM methylmercury. While a significant decrease in glutathione levels was observed in M group, it was not seen in EM group. A significant increase in the protein carbonyl levels was detected in T group. A similar increase was observed in the TM and TT groups in which testosterone was dominant. It was determined that methylmercury, but not thimerosal, caused significant DNA damage and in TT group. The results showed that both thimerosal and methylmercury are toxic on SH-SY5Y cells and toxic effects of methylmercury are more severe than thimerosal. It has been determined that testosterone and estradiol alter the toxic effects of thimerosal and methylmercury., (© 2021 John Wiley & Sons, Ltd.)

In this study, we aimed to evaluate possible toxic effects of thimerosal, aluminum and combination of thimerosal and aluminum in SH-SY5Y cells. Inhibitory concentrations were determined by MTT assay; reactive oxygen species (ROS) were determined by a fluorometric kit and antioxidant/oxidant parameters were measured by spectrophotometric kits. Nuclear factor erythroid 2-associated factor 2 (Nrf2), norepinephrine (NE), dopamine transporter (DAT) and dopamine beta β-hydroxylase (DBH) levels were measured by sandwich ELISA kits while 8-hydroxy deoxyguanosine (8-OHdG) and dopamine levels were determined by competitive ELISA kits. Thimerosal (1.15 μM) and aluminum (362 μM) were applied to cells at inhibitory concentrations 20 (IC 20 s) for 24 h. ROS increased significantly in cells aluminum- and aluminum+thimerosal-treated cells. Glutathione levels decreased in aluminum group while total antioxidant capacity and protein oxidation levels increased significantly in aluminum and aluminum+thimerosal groups. Lipid peroxidation increased significantly in groups treated with aluminum and aluminum+thimerosal. Nrf2 levels and DNA damage were significantly higher in all groups while dopamine levels significantly increased in cells treated with thimerosal and aluminum+thimerosal, DAT levels were found to be higher in all experimental groups compared to the control. These findings showed that both thimerosal and aluminum can change oxidant/antioxidant status, cause DNA damage, alter dopamine and DAT levels. Changes seen in cells treated with combined exposure to aluminum and thimerosal are more pronounced. Special care should be taken while vaccinating sensitive populations and safer alternatives for aluminum and thimerosal should used.