Sunscreen application is the main strategy used to prevent the maladies inflicted by ultraviolet (UV) radiation. Despite the continuously increasing frequency of sunscreen use worldwide, the prevalence of certain sun exposure-related pathologies, mainly malignant melanoma, is also on the rise. In the past century, a variety of protective agents against UV exposure have been developed. Physical filters scatter and reflect UV rays and chemical filters absorb those rays. Alongside the evidence for increasing levels of these agents in the environment, which leads to indirect exposure of wildlife and humans, recent studies suggest a toxicological nature for some of these agents. Reviews on the role of these agents in developmental and endocrine impairments (both pathology and related mechanisms) are based on both animal and human studies, yet information regarding the potential neurotoxicity of these agents is scant. In this review, data regarding the neurotoxicity of several organic filters: octyl methoxycinnamate, benzophenone-3 and -4, 4-methylbenzylidene camphor, 3-benzylidene camphor and octocrylene, and two allowed inorganic filters: zinc oxide and titanium dioxide, is presented and discussed. Taken together, this review advocates revisiting the current safety and regulation of specific sunscreens and investing in alternative UV protection technologies.

Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits significant toxicity in humans. The accumulation of MeHg through the daily consumption of large predatory fish poses potential health risks, and the central nervous system (CNS) is the primary target of toxicity. Despite well-described neurobehavioral effects (i.e., motor impairment), the mechanisms of MeHg-induced toxicity are not completely understood. However, several lines of evidence point out the oxidative stress as an important molecular mechanism in MeHg-induced intoxication. Indeed, MeHg is a soft electrophile that preferentially interacts with nucleophilic groups (mainly thiols and selenols) from proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress, which can produce damage by several interacting mechanisms, impairing the function of various molecules (i.e., proteins, lipids, and nucleic acids), potentially resulting in modulation of different cellular signal transduction pathways. This review summarizes the general aspects regarding the interaction between MeHg with regulators of the antioxidant response system that are rich in thiol and selenol groups such as glutathione (GSH), and the selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). A particular attention is directed towards the role of the PI3K/Akt signaling pathway and the nuclear transcription factor NF-E2-related factor 2 (Nrf2) in MeHg-induced redox imbalance.

Metabolic syndrome (MetS) is an important public health issue that affects millions of people around the world and is growing to pandemic-like proportions. This syndrome is defined by the World Health Organization (WHO) as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Moreover, the etiology of MetS is multifactorial, involving many environmental factors, including toxicant exposures. Several studies have associated MetS with heavy metals exposure, which is the focus of this review. Environmental and/or occupational exposure to heavy metals are a major risk, contributing to the development of chronic diseases. Of particular note, toxic metals such as mercury, lead, and cadmium may contribute to the development of MetS by altering oxidative stress, IL-6 signaling, apoptosis, altered lipoprotein metabolism, fluid shear stress and atherosclerosis, and other mechanisms. In this review, we discuss the known and potential roles of heavy metals in MetS etiology as well as potential targeted pathways that are associated with MetS. Furthermore, we describe how new approaches involving proteomic and transcriptome analysis, as well as bioinformatic tools, may help bring about an understanding of the involvement of heavy metals and metalloids in MetS.

Manganese (Mn) is an essential trace element, but insufficient or excessive bodily amounts can induce neurotoxicity. Mn can directly increase neuronal insulin and activate insulin-like growth factor (IGF) receptors. As an important cofactor, Mn regulates signaling pathways involved in various enzymes. The IGF signaling pathway plays a protective role in the neurotoxicity of Mn, reducing apoptosis in neurons and motor deficits by regulating its downstream protein kinase B (Akt), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR). In recent years, some new mechanisms related to neuroinflammation have been shown to also play an important role in Mn-induced neurotoxicity. For example, DNA-sensing receptor cyclic GMP–AMP synthase (cCAS) and its downstream signal efficient interferon gene stimulator (STING), NOD-like receptor family pyrin domain containing 3(NLRP3)-pro-caspase1, cleaves to the active form capase1 (CASP1), nuclear factor κB (NF-κB), sirtuin (SIRT), and Janus kinase (JAK) and signal transducers and activators of the transcription (STAT) signaling pathway. Moreover, autophagy, as an important downstream protein degradation pathway, determines the fate of neurons and is regulated by these upstream signals. Interestingly, the role of autophagy in Mn-induced neurotoxicity is bidirectional. This review summarizes the molecular signaling pathways of Mn-induced neurotoxicity, providing insight for further understanding of the mechanisms of Mn.

Methylmercury (MeHg) is an environmental pollutant that affects primarily the central nervous system (CNS), causing neurological alterations. An early symptom of MeHg poisoning is the loss of body weight and appetite. Moreover, the CNS has an important role in controlling energy homeostasis. It is known that in the hypothalamus nutrient and hormonal signals converge to orchestrate control of body weight and food intake. In this study, we investigated if MeHg is able to induce changes in the expression of key hypothalamic neuropeptides that regulate energy homeostasis. Thus, hypothalamic neuronal mouse cell line GT 1-7 was treated with MeHg at different concentrations (0, 0.5, 1, and 5 µM). MeHg induced the expression of the anorexigenic neuropeptide pro-omiomelanocortin (Pomc) and the orexigenic peptide Agouti-related peptide (Agrp) in a concentration-dependent manner, suggesting deregulation of mechanisms that control body weight. To confirm these in vitro observations, 8-week-old C57BL/6J mice (males and females) were exposed to MeHg in drinking water, modeling the most prevalent exposure route to this metal. After 30-day exposure, no changes in body weight were detected. However, MeHg treated males showed a significant decrease in fat depots. Moreover, MeHg affected the expression of hypothalamic neuropeptides that control food intake and body weight in a gender- and dose-dependent manner. Thus, MeHg increases Pomc mRNA only in males in a dose-dependent way, and it does not have effects on the expression of Agrp mRNA. The present study shows, for first time, that MeHg is able to induce changes in hypothalamic neuropeptides that regulate energy homeostasis, favoring an anorexigenic/catabolic profile.

Manganese (Mn) and iron (Fe) are essential trace metals. Both are essential for multiple physiological processes, including brain function, metabolism, and cellular respiration. However, excessive exposure to these metals can have detrimental health effects, particularly in occupational exposures, such as mining, welding, battery production, and iron and steel manufacturing. Mn and Fe accumulate in astrocytes, especially in brain regions involved in motor control and cognition, such as the substantia nigra and globus pallidus in the basal ganglia. Excessive exposure to Mn and Fe induces oxidative stress, neuronal damage and neurodegeneration, and has been implicated in various neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here, we investigated the effects of combined Mn and Fe exposure on C8-D1A astrocytic cells and explored the associated oxidative stress pathways. Our results demonstrated that Mn exposure decreased Superoxide dismutase 2 ( Sod2) mRNA expression and one of its upstream regulators, Signal Transducer and Activator of Transcription 3 (STAT3) protein and gene levels, associated with an increase in oxidative stress, whereas Fe exposure had no effect on this pathway. Interestingly, combined Mn and Fe exposure decreased reactive oxygen species (ROS) levels and upregulated the expression of the antioxidant gene NAD(P)H quinone dehydrogenase 1 (NQO1) compared to Mn and Fe exposure alone. Our findings suggest that combined Mn and Fe exposure activate the Nuclear factor erythroid 2-related factor 2 (NRF2)/NQO1 antioxidant signaling pathway in C8-D1A astrocytic cells, mitigating oxidative stress and protecting cells from damage. By understanding these mechanisms, novel therapeutic targets for neurodegenerative diseases associated with occupational metal exposures may be identified.