Search

The aim of the present investigation was to determine the effects of sodium fluoride (NaF) on aluminum-induced toxicity in PC12 cells, a rat pheochromocytoma cell line, including cell death and changes in apoptosis, mitochondrial membrane potential (MMP), and oxidative stress. Aluminum (Al) and the fluoride ion (F) are known as plausible pathological factors in the pathogenesis of neurodegenerative disease. Conflicting results have been reported on the interaction of fluoride and aluminum on cell toxicity. PC12 cells were treated with various concentrations of aluminum maltolate (Almal) in the presence and absence of NaF (50-2400 µM) in vitro. A MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to determine cell viability. 7AAD/annexin-V and 2',7'-dichlorofluorescin diacetate (DCFDA) flow cytometric methods were used to quantify the effects of NaF on Al-induced apoptosis and reactive oxygen species (ROS) generation, respectively. The mitochondrial membrane potential (MMP) was monitored using the retention of rhodamine 123. Catalase activity was determined by measuring the rate of H2O2 decomposition. Almal exposure increased cell death dose dependently and significantly (IC50=1090 µM). ROS generation and apoptosis were increased while MMP and catalase activity were reduced following treatment with Almal. NaF ameliorated the Almal-induced cell toxicity in low concentrations while augmenting the Almal effects at high concentrations. The present data suggest F has antagonistic impacts on Al-induced cell toxicity in low concentrations while acting synergistically with Al to induce cell toxicity at high concentrations. [ABSTRACT FROM AUTHOR]

Sodium benzoate (SB) is one of the food additives and preservatives that prevent the growth of fungi and bacteria. SB has been shown to improve the symptoms of neurodegenerative disease such as Alzheimer's disease. The aim of this study was to evaluate the effect of SB on the cell survival and cellular antioxidant indices after exposure to aluminum maltolate (Almal) in PC12 cell line as a model of neurotoxicity. The cells exposed to different concentrations of SB (0.125 to 3 mg/mL) in the presence of Almal (500 µM) and cell viability, the level of reactive oxygen species (ROS), glutathione content and catalase activity were measured. The results showed that low concentrations of SB caused an increase in the cell survival, but cell viability was reduced in high concentrations. SB could neither prevent the level of ROS production nor change glutathione content. SB (0.5 mg/mL) significantly increased the catalase enzyme activity as compared to the Almal. This study suggested that SB did not completely protect the cell to aluminuminduced free radicals toxicity. Possibly SB improves the symptoms of neurodegenerative disease by other mechanisms. [ABSTRACT FROM AUTHOR]

Objective(s): The role of aluminum (Al) in the pathogenesis of neurodegenerative diseases has been implicated in several studies. However, the exact mechanisms of cytotoxic effects of Al have not been elucidated yet. The aim of this study was to investigate the effect of L-type calcium channel antagonist, nimodipine (NM), and lithium chloride (LiCl) on Al-induced toxicity in PC12 cells. Materials and Methods: PC12 cells were treated with Al-maltolate (Almal) in the presence and absence of different concentrations of NM (50-150 μm) and/or LiCl (0.5-1.0 mM) for 48 hr. Cell viability, apoptosis, and catalase (CAT) activity, a marker of oxidative stress, were then measured using MTT, flow cytometry and enzyme assay, respectively. Results: The results showed that Almal, dose dependently induced cell death, apoptosis and CAT activity in the PC12 cells. NM significantly increased cell viability and decreased apoptosis and CAT activity of Almal-treated cells in a dose dependent mode. LiCl reduced CAT activity and increased cell viability in Almal-treated cells, without significant effect on apoptosis (P=0.74). Conclusion: These findings suggest that NM and Li may have benefits in the prevention of Al-induced cytotoxicity through decreasing oxidative stress. [ABSTRACT FROM AUTHOR]

Increased expression and aggregation of α-synuclein (α-syn) protein plays a critical role in mediating the toxic effects of a number of neurodegenerative substances including metals. Thus, knockdown expression of α-syn is proposed as a possible modality for treatment of Parkinson disease (PD). Aluminum (Al) is a neurotoxic metal that contributes to pathogenesis of PD. The aim of this study was to investigate the role of α-syn protein in mediating Al-induced toxicity in PC12 cells. Specific α-syn small interference RNA (siRNA) was applied to knockdown the expression of α-syn protein in PC12 cells. The effects of different concentrations of Al-maltolate (Almal) were then evaluated on cell viability and oxidative stress in the α-syn downregulated cells. The results showed that Almal dose dependently induced apoptosis and increased malondialdehyde (MDA) and catalase activity in PC12 cells. Downregulation of α-syn protein significantly increased cell viability and decreased oxidative markers in Almal-treated cells. These findings suggest that α-syn protein may mediate Al-induced apoptosis and oxidative stress in PC12 cells. [ABSTRACT FROM AUTHOR]