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Current Neuropharmacology 2019Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. It has recognized activity as an endocrine-disrupting chemical and has suspected roles as a... (Review)
Review
BACKGROUND
Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. It has recognized activity as an endocrine-disrupting chemical and has suspected roles as a neurological and reproductive toxicant. It interferes in steroid signaling, induces oxidative stress, and affects gene expression epigenetically. Gestational, perinatal and neonatal exposures to BPA affect developmental processes, including brain development and gametogenesis, with consequences on brain functions, behavior, and fertility.
METHODS
This review critically analyzes recent findings on the neuro-toxic and reproductive effects of BPA (and its analogues), with focus on neuronal differentiation, synaptic plasticity, glia and microglia activity, cognitive functions, and the central and local control of reproduction.
RESULTS
BPA has potential human health hazard associated with gestational, peri- and neonatal exposure. Beginning with BPA's disposition, this review summarizes recent findings on the neurotoxicity of BPA and its analogues, on neuronal differentiation, synaptic plasticity, neuroinflammation, neuro-degeneration, and impairment of cognitive abilities. Furthermore, it reports the recent findings on the activity of BPA along the HPG axis, effects on the hypothalamic Gonadotropin Releasing Hormone (GnRH), and the associated effects on reproduction in both sexes and successful pregnancy.
CONCLUSION
BPA and its analogues impair neuronal activity, HPG axis function, reproduction, and fertility. Contrasting results have emerged in animal models and human. Thus, further studies are needed to better define their safety levels. This review offers new insights on these issues with the aim to find the "fil rouge", if any, that characterize BPA's mechanism of action with outcomes on neuronal function and reproduction.
Topics: Animals; Benzhydryl Compounds; Humans; Neurons; Phenols; Reproduction
PubMed: 31362658
DOI: 10.2174/1570159X17666190726112101 -
International Journal of Molecular... Aug 2021Prenatal alcohol exposure (PAE) can have immediate and long-lasting toxic and teratogenic effects on an individual's development and health. As a toxicant, alcohol can... (Review)
Review
Prenatal alcohol exposure (PAE) can have immediate and long-lasting toxic and teratogenic effects on an individual's development and health. As a toxicant, alcohol can lead to a variety of physical and neurological anomalies in the fetus that can lead to behavioral and other impairments which may last a lifetime. Recent studies have focused on identifying mechanisms that mediate the immediate teratogenic effects of alcohol on fetal development and mechanisms that facilitate the persistent toxic effects of alcohol on health and predisposition to disease later in life. This review focuses on the contribution of epigenetic modifications and intercellular transporters like extracellular vesicles to the toxicity of PAE and to immediate and long-term consequences on an individual's health and risk of disease.
Topics: Adolescent; Adolescent Development; Adult; Epigenesis, Genetic; Ethanol; Extracellular Vesicles; Female; Fetal Development; Gene Expression Regulation; Humans; Pregnancy; Prenatal Exposure Delayed Effects; Teratogenesis
PubMed: 34445488
DOI: 10.3390/ijms22168785 -
Reproductive Toxicology (Elmsford, N.Y.) Aug 2018Known endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. Its structural analogs: bisphenol S (BPS), bisphenol F (BPF),... (Review)
Review
Known endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. Its structural analogs: bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) are increasingly being used in consumer products. However, these analogs may exert similar adverse effects on the reproductive system, and their toxicological data are still limited. This mini-review examined studies on both BPA and BPA analog exposure and reproductive toxicity. It outlines the current state of knowledge on human exposure, toxicokinetics, endocrine activities, and reproductive toxicities of BPA and its analogs. BPA analogs showed similar endocrine potencies when compared to BPA, and emerging data suggest they may pose threats as reproductive hazards in animal models. While evidence based on epidemiological studies is still weak, we have utilized current studies to highlight knowledge gaps and research needs for future risk assessments.
Topics: Animals; Benzhydryl Compounds; Endocrine Disruptors; Female; Humans; Male; Phenols; Reproductive Health
PubMed: 29925041
DOI: 10.1016/j.reprotox.2018.06.005 -
International Journal of Environmental... Mar 2019Mercury (Hg) has been identified as one of the most toxic nonradioactive materials known to man. Although mercury is a naturally occurring element, anthropogenic mercury... (Review)
Review
Mercury (Hg) has been identified as one of the most toxic nonradioactive materials known to man. Although mercury is a naturally occurring element, anthropogenic mercury is now a major worldwide concern and is an international priority toxic pollutant. It also comprises one of the primary constituents of dental amalgam fillings. Even though dental mercury amalgams have been used for almost two centuries, its safety has never been tested or proven in the United States by any regulatory agency. There has been an ongoing debate regarding the safety of its use since 1845, and many studies conclude that its use exposes patients to troublesome toxicity. In this review, we present in an objective way the danger of dental amalgam to human health based on current knowledge. This dilemma is addressed in terms of an integrated toxicological approach by focusing on four mayor issues to show how these interrelate to create the whole picture: (1) the irrefutable constant release of mercury vapor from dental amalgams which is responsible for individual chronic exposure, (2) the evidence of organic mercury formation from dental amalgam in the oral cavity, (3) the effect of mercury exposure on gene regulation in human cells which supports the intrinsic genetic susceptibility to toxicant and, finally, (4) the availability of recent epidemiological data supporting the link of dental amalgams to diseases such as Alzheimer's and Parkinson.
Topics: Dental Amalgam; Humans; Mercury; United States
PubMed: 30909378
DOI: 10.3390/ijerph16061036 -
Toxics Nov 2023Plastics, including microplastics, have generally been regarded as harmful to organisms because of their physical characteristics. There has recently been a call to... (Review)
Review
Plastics, including microplastics, have generally been regarded as harmful to organisms because of their physical characteristics. There has recently been a call to understand and regard them as persistent, bioaccumulative, and toxic. This review elaborates on the reasons that microplastics in particular should be considered as "toxic pollutants". This view is supported by research demonstrating that they contain toxic chemicals within their structure and also adsorb additional chemicals, including polychlorinated biphenyls (PCBs), pesticides, metals, and polycyclic aromatic hydrocarbons (PAHs), from the environment. Furthermore, these chemicals can be released into tissues of animals that consume microplastics and can be responsible for the harmful effects observed on biological processes such as development, physiology, gene expression, and behavior. Leachates, weathering, and biofilm play important roles in the interactions between microplastics and biota. Global policy efforts by the United Nations Environmental Assembly via the international legally binding treaty to address global plastic pollution should consider the designation of harmful plastics (e.g., microplastics) with associated hazardous chemicals as toxic pollutants.
PubMed: 37999586
DOI: 10.3390/toxics11110935 -
Toxics Sep 2021Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of... (Review)
Review
Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of substances and by different mechanisms. Toxic agents are numerous and can be distinguished between drugs, recreational agents, heavy metals, industrial agents, pesticides, warfare agents, biologic substances and venoms. Toxic agents reach the nervous system by ingestion, transcutaneously, via the mucous membranes, parenterally and by aerosols. The most frequent types are cumulative toxicities. Other types are acute or delayed toxicities. Pathogenetic mechanisms range from a specific toxic substance profile causing axonal or demyelinating lesions, towards ion channel interferences, immune-mediated mechanisms and a number of different molecular pathways. In addition, demyelination, focal lesions and small fiber damage may occur. Clinically, neurotoxicity presents most frequently as axonal symmetric neuropathies. In this work, we present a panoramic view of toxic neuropathy, in terms of symptoms, causes, mechanisms and classification.
PubMed: 34564369
DOI: 10.3390/toxics9090218 -
Toxics Oct 2022Large amounts of enriched cadmium (Cd) in the environment seriously threatens the healthy and sustainable development of the aquaculture industry and greatly restricts... (Review)
Review
Large amounts of enriched cadmium (Cd) in the environment seriously threatens the healthy and sustainable development of the aquaculture industry and greatly restricts the development of the food processing industry. Studying the distribution and toxic effects of Cd in fish, as well as the possible toxic effects of Cd on the human body, is very significant. A large number of studies have shown that the accumulation and distribution of Cd in fish are biologically specific, cause tissue differences, and seriously damage the integrity of tissue structure and function, the antioxidant defense system, the reproductive regulation system, and the immune system. The physiological, biochemical, enzyme, molecular, and gene expression levels change with different concentrations and times of Cd exposure, and these changes are closely related to the target sites of Cd action and tissues in fish. Therefore, the toxic effects of Cd on fish occur with multiple tissues, systems, and levels.
PubMed: 36287901
DOI: 10.3390/toxics10100622 -
Archives of Pharmacal Research Mar 2020Liver plays essential roles in the metabolism of many endogenous chemicals and exogenous toxicants. Mechanistic studies in liver have been at the forefront of efforts to... (Review)
Review
Liver plays essential roles in the metabolism of many endogenous chemicals and exogenous toxicants. Mechanistic studies in liver have been at the forefront of efforts to probe the roles of bioactivation and detoxication of environmental toxins and toxicants in hepatotoxicity. Moreover, idiosyncratic hepatoxicity remains a key barrier in the clinical development of drugs. The now vast Nrf2 field emerged in part from biochemical and molecular studies on chemical inducers of hepatic detoxication enzymes and subsequent characterization of the modulation of drug/toxicant induced hepatotoxicities in mice through disruption of either Nrf2 or Keap1 genes. In general, loss of Nrf2 increases the sensitivity to such toxic chemicals, highlighting a central role of this transcription factor and its downstream target genes as a modifier to chemical stress. In this review, we summarize the impact of Nrf2 on the toxicology of multiple hepatotoxicants, and discuss efforts to utilize the Nrf2 response in predictive toxicology.
Topics: Animals; Chemical and Drug Induced Liver Injury; Humans; Liver; NF-E2-Related Factor 2
PubMed: 31782059
DOI: 10.1007/s12272-019-01192-3 -
Integrative Medicine (Encinitas, Calif.) Feb 2020The worldwide prevalence of obesity has near tripled between 1975 and 2016. Diabetes was the direct cause of an estimated 1.6 million deaths in 2015. Diabetogens,... (Review)
Review
The worldwide prevalence of obesity has near tripled between 1975 and 2016. Diabetes was the direct cause of an estimated 1.6 million deaths in 2015. Diabetogens, otherwise known as toxicants that cause insulin resistance in animal models and humans as a result of pancreatic β-cell damage include the persistent organochlorine pesticides -nonachlor, oxychlordane, and DDE -the main metabolite of DDT, as well as another class of persistent organic pollutants, polychlorinated biphenyls (PCBs). Other toxicants that are now considered diabetogens: BPA, arsenic, phthalates, perfluorinates (PFOS), diethyl hexyl phthalate (DEHP), and dioxin (TCDD) are commonly found in the blood and urine in the CDC NHANES populations and presumed to also be commonly found in the U.S. population as a whole. A review of the literature on the risk for diabetes in epidemiologic studies considering these toxicants, challenges for clinicians using lab testing for these diabetogens, and the necessary interventions for lowering body burden of persistent toxicants are discussed.
PubMed: 32549860
DOI: No ID Found -
Computational and Structural... 2023Developmental toxicology is the field of study that examines the effects of chemical and physical agents on developing organisms. By using principles of systems biology... (Review)
Review
Developmental toxicology is the field of study that examines the effects of chemical and physical agents on developing organisms. By using principles of systems biology and bioengineering, a systems bioengineering approach could be applied to study the complex interactions between developing organisms, the environment, and toxic agents. This approach would result in a holistic understanding of the effects of toxic agents on organisms, by considering the interactions between different biological systems and the impacts of toxicants on those interactions. It would be useful in identifying key biological pathways and mechanisms affected by toxic agents, as well as in the development of predictive models to assess potential risks of exposure to toxicants during development. In this review, we discuss the relevance of systems bioengineering to the field of developmental toxicity and provide up-to-date examples that illustrate the use of engineering principles for this application.
PubMed: 38213895
DOI: 10.1016/j.csbj.2023.06.005