Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential. In light of the adverse effects that have been already documented in biota and human populations or that might occur in absence of prompt interventions, the competent authorities in matter of health and environment protection, the industries as well as scientists are cooperating to identify the most appropriate regulatory measures, substitution plans and remediation technologies to mitigate PFAS impacts. In this review, starting from PFAS chemistry, uses and environmental fate, we summarize the current knowledge on PFAS occurrence in different environmental media and their effects on living organisms, with a particular emphasis on humans. Also, we describe present and provisional legislative measures in the European Union framework strategy to regulate PFAS manufacture, import and use as well as some of the most promising treatment technologies designed to remediate PFAS contamination in different environmental compartments.

Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resistance to oxidants, serves as one of the key defensive factors against a range of pathological processes such as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals. An increase in human exposure to toxic metals via air, food, and water has been recently observed, which is mainly due to anthropogenic activities. The relationship between environmental exposure to heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well as metaloid arsenic (As), and transition metal chromium (Cr), and the development of various human diseases has been extensively investigated. Their ability to induce reactive oxygen species (ROS) production through direct and indirect actions and cause oxidative stress has been documented in various organs. Taking into account that Nrf2 signaling represents an important pathway in maintaining antioxidant balance, recent research indicates that it can play a dual role depending on the specific biological context. On one side, Nrf2 represents a potential crucial protective mechanism in metal-induced toxicity, but on the other hand, it can also be a trigger of metal-induced carcinogenesis under conditions of prolonged exposure and continuous activation. Thus, this review aims to summarize the state-of-the-art knowledge regarding the functional interrelation between the toxic metals and Nrf2 signaling.

Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of “hyperglycemic” metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.

Phthalates and bisphenol A, classified as endocrine disruptors, have weak estrogenic, anti-androgenic properties, and affect thyroid hormone regulation. The aim of this study on male rats was to compare the subacute toxic effects of low doses of single compounds (bis (2 –ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA)) with the effects of their mixture through different biochemical, hormonal, and hematological parameters. Rats were divided into five experimental groups: Control (corn oil), DEHP (50 mg/kg b.w./day), DBP (50 mg/kg b.w./day), BPA (25 mg/kg b.w./day), and MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA). Animals were sacrificed after 28 days of oral treatment and blood was collected for further analysis. The results demonstrated that the mixture produced significant changes in lipid profile, liver-related biochemical parameters, and glucose level. Furthermore, the opposite effects of single substances on the thyroxine level have been shown in comparison with the mixture, as well as a more pronounced effect of the mixture on testosterone level. This study contributes to the body of knowledge on the toxicology of mixtures and gives one more evidence of the paramount importance of mixture toxicity studies, especially in assessing the endocrine disruptive effects of chemicals.

Sulforaphane (SFN), which is a hydrolysis product from glucoraphanin, a compound found in cruciferous vegetables, has been studied for its potential health benefits, particularly in disease prevention and treatment. SFN has proven to be effective in combating different types of cancer by inhibiting the proliferation of tumors and triggering apoptosis. This dual action has been demonstrated to result in a reduction in tumor size and an enhancement of survival rates in animal models. SFN has also shown antidiabetic and anti-obesity effects, improving glucose tolerance and reducing fat accumulation. SFN’s ability to activate Nrf2, a transcription factor regulating oxidative stress and inflammation in cells, is a primary mechanism behind its anticancerogenic and antidiabetic effects. Its antioxidant, anti-inflammatory, and anti-apoptotic properties are also suggested to provide beneficial effects against neurodegenerative diseases. The potential health benefits of SFN have led to increased interest in its use as a dietary supplement or adjunct to chemotherapy, but there are insufficient data on its efficacy and optimal doses, as well as its safety. This review aims to present and discuss SFN’s potential in treating various diseases, such as cancer, diabetes, cardiovascular diseases, obesity, and neurodegenerative diseases, focusing on its mechanisms of action. It also summarizes studies on the pharmacological and toxicological potential of SFN in in vitro and animal models and explores its protective role against toxic compounds through in vitro and animal studies.