Nitrites are ubiquitous environmental contaminants present in drinking water and foods. Nitrosamines can be formed endogenously from nitrate and nitrite and secondary amines or may be present in food, tobacco smoke, and drinking water. The major goal of this work was to evaluate the cytotoxic, reactive oxygen species (ROS)-producing and genotoxic effects of nitrite and nitrosamines and the possible protection by ascorbic acid in HepG2 cells. It was found that nitrite, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitrosomorpholine (NMOR) decreased cell viability, increased intracellular ROS production, and caused genotoxicity. Compared to untreated cells as determined by alkaline Comet assay, nitrite, NDMA, NDEA, and NMOR raised the tail intensity up to 1.18-, 3.79-, 4.24-, and 4.16-fold, respectively. Ascorbic acid (AA, 10 μM) increased cell viability and reduced ROS production significantly (p < 0.05). Additionally, AA treatment decreased the tail intensity caused by nitrite, NDMA, NDEA, and NMOR to 33.74%, 58.6%, 44.32%, and 43.97%, respectively. It can be concluded that ascorbic acid was able to reduce both tail intensity and tail moment in all of the nitrosamine treatments, particularly in NDMA. AA protected HepG2 cells against genotoxic effects caused by nitrosamines. This protection might be through different mechanisms, some of which are not still understood in depth. The future interest will be to understand which pathways are influenced by antioxidants, particularly by AA, and the outcomes of this prevention in other cell line types.

Aluminum (Al) is an environmentally abundant metal that is not essential for life. There is considerable evidence that Al as a neurotoxic xenobiotic may play a role in the pathogenesis of neurodegenerative diseases like Alzheimer’s disease (AD). Exposure to aluminum has been shown to cause neuronal damage that resembles the symptoms of AD. In this review, we will summarize recent data about Al as the possible risk of incidence of AD. Then glycogen synthase kinase-3 beta (GSK3β) contributes to the hyperphosphorylation of Tau protein, the main component of neurofibrillary tangles, one of the hallmarks of AD as one of the mechanisms behind Al neurotoxicity will be covered. Overall, there is still a need for epidemiological studies and more in vivo and in vitro studies to determine the exact mechanisms of its neurotoxicity and the role of GSK3β in both Al toxic effect and AD.

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is used in a variety of consumer products such as electronic equipment, fire extinguishers, furniture, plastics, textiles, and kitchen hoods. Most studies show that the TBBPA production process and TBBPA in industrial and urban sewage waste result in extensive human exposure and environmental contamination. TBBPA can accumulate in organisms, particularly aquatic life, and is classified as a group 2A carcinogen (likely carcinogenic to humans) by the International Agency for Research on Cancer. This compound produces low acute toxicity, but chronic exposure may produce serious consequences. In this review, we focus on TBBPA toxicity by discussing results of various studies that were published in the last two decades. Studies show that TBBPA acts as an endocrine disruptor, causing neurobehavioral and immunotoxic effects, oxidative stress, and apoptosis. Although several experiments were performed in vitro and in vivo, human data are lacking, and thus, chronic toxic effects of TBBPA on humans are not well known, particularly in sensitive populations including pregnant women, newborns, children, and the elderly. Epidemiological studies that comprehensively assess TBBPA levels in biological fluids of different populations and in different pathological conditions are needed. Research on the impact of TBBPA, particularly regarding endocrine disorders and cancer, must also be performed.