It is well known that the excessive production of reactive oxygen species (ROS) can lead to the peroxidation of membrane lipids, glycation/oxidation/nitration of proteins, inactivation of enzymes, DNA mutation and damage, and other alterations in the subcellular components [...]
Due to their unique properties, perfluorinated substances (PFAS) are widely used in multiple industrial and commercial applications, but they are toxic for animals, humans included. This review presents some available data on the PFAS environmental distribution in the world, and in particular in Europe and in the Veneto region of Italy, where it has become a serious problem for human health. The consumption of contaminated food and drinking water is considered one of the major source of exposure for humans. Worldwide epidemiological studies report the negative effects that PFAS have on human health, due to environmental pollution, including infertility, steroid hormone perturbation, thyroid, liver and kidney disorders, and metabolic disfunctions. In vitro and in vivo researches correlated PFAS exposure to oxidative stress effects (in mammals as well as in other vertebrates of human interest), produced by a PFAS-induced increase of reactive oxygen species formation. The cellular antioxidant defense system is activated by PFAS, but it is only partially able to avoid the oxidative damage to biomolecules.
Heavy metal pollution is known to be widespread in the sediments of the Lagoon of Venice. Therefore, physiological parameters influenced by this form of contamination were examined. The bivalve molluscs blue mussel (Mytilus galloprovincialis), ark clam (Scapharca inaequivalvis), and Japanese littleneck (Tapes philippinarum) were sampled in two sites (Marghera, Chioggia) every 3 months for 1 year. The digestive gland and gills of each bivalve were analyzed. The concentrations of essential and nonessential metals (including chromium, manganese, iron, cobalt, nickel, copper, zinc, and cadmium) were determined. Because glutathione and metallothioneins (MTs) are involved in metal homeostasis and detoxification, their concentrations were evaluated in relation to metal concentrations. Results show that (1) all three studied species accumulate metals to a considerable extent, with some species-specific differences between the digestive gland and gills; (2) gills are a good tissue to evaluate pollution by examining the MT content. In particular, the correlation between Zn and MT levels in the gills indicates that M. galloprovincialis and S. inaequivalvis are sentinel organisms and can be used specifically for Zn pollution; (3) T. philippinarum accumulates Cu in the digestive gland more readily than the other two bivalves and therefore has the highest MT.
Metals can directly or indirectly cause an increase in reactive oxygen species (ROS) accumulation in cells, and this may result in programmed cell death. A number of previous studies have shown that zinc (Zn) modulates mitogenic activity via several signalling pathways, such as AKT, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF -κB), AP-1 and p53. The exact role that Zn plays in the regulation of apoptosis remains ambiguous. Intracellular free Zn modulates p53 activity and stability, and excess Zn alters the p53 protein structure and down-regulates p53's binding to DNA. Copper (Cu) accumulation causes apoptosis that seems to be mediated by DNA damage and subsequent p53 activation. Cu can also displace Zn from its normal binding site on p53, resulting in abnormal protein folding and disruption of p53 function. In spite of the induction of the tumour suppressor p53, hepatic Cu accumulation significantly increases the risk of cancerous neoplasm both in humans and rats, suggesting that p53 function may be impaired in these cells. It is generally understood that imbalances in Cu and Zn levels may lead to a higher prevalence of p53 mutations. An increased number of p53 mutations have been found in liver samples from Wilson's disease (WD) patients. High levels of the p53 mutation most probably contribute to the pathogenesis of cancer in individuals with WD, but the cause and effect are not clear. The protein p53 also plays a crucial role in the transcriptional regulation of metallothionein, which indicates a novel regulatory role for p53. This review discusses the central role of p53 and the redox-inert metal Zn in the cellular stress responses induced by the redox active biometal Cu.
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