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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 -
Journal of Alzheimer's Disease : JAD 2020Alzheimer's disease and related dementias lack effective treatment or cures and are major public health challenges. Risk for Alzheimer's disease and related dementias is... (Review)
Review
Alzheimer's disease and related dementias lack effective treatment or cures and are major public health challenges. Risk for Alzheimer's disease and related dementias is partially attributable to environmental factors. The heavy metals lead, cadmium, and manganese are widespread and persistent in our environments. Once persons are exposed to these metals, they are adept at entering cells and reaching the brain. Lead and cadmium are associated with numerous health outcomes even at low levels of exposure. Although manganese is an essential metal, deficiency or environmental exposure or high levels of the metal can be toxic. In cell and animal model systems, lead, cadmium, and manganese are well documented neurotoxicants that contribute to canonical Alzheimer's disease pathologies. Adult human epidemiologic studies have consistently shown lead, cadmium, and manganese are associated with impaired cognitive function and cognitive decline. No longitudinal human epidemiology study has assessed lead or manganese exposure on Alzheimer's disease specifically though two studies have reported a link between cadmium and Alzheimer's disease mortality. More longitudinal epidemiologic studies with high-quality time course exposure data and incident cases of Alzheimer's disease and related dementias are warranted to confirm and estimate the proportion of risk attributable to these exposures. Given the widespread and global exposure to lead, cadmium, and manganese, even small increases in the risks of Alzheimer's disease and related dementias would have a major population impact on the burden on disease. This article reviews the experimental and epidemiologic literature of the associations between lead, cadmium, and manganese on Alzheimer's disease and related dementias and makes recommendations of critical areas of future investment.
Topics: Alzheimer Disease; Animals; Cadmium; Dementia; Environmental Exposure; Humans; Manganese; Metals, Heavy
PubMed: 32651318
DOI: 10.3233/JAD-200282 -
Environmental Health and Preventive... Sep 2019Hookah or waterpipe smoking or use is an emerging trend in the US population, especially among the youth. The misperception of hookah being less harmful than cigarettes... (Review)
Review
Hookah or waterpipe smoking or use is an emerging trend in the US population, especially among the youth. The misperception of hookah being less harmful than cigarettes and the availability of different but "appealing" flavors are considered among the main reasons for this trend. Hookah users however are exposed to many of the same toxic compounds/by-products as cigarette users, but at dramatically higher levels, which might lead to more severe negative health effects. In fact, hookah users are at risks of infections, cancers, lung disease, and other medical conditions. Moreover, because of the overlapping toxicant/chemical profile to conventional cigarettes, hookah smoke effects on the cardiovascular system are thought to be comparable to those of conventional cigarettes. A major source of tobacco addiction is nicotine, whose levels in hookah are extremely variable as they depend on the type of tobacco used. Taken together, in this review of literature, we will provide insights on the negative health effects of hookah in general, with a focus on what is known regarding its impact on the cardiovascular system.
Topics: Cardiovascular Diseases; Electronic Nicotine Delivery Systems; Hazardous Substances; Humans; Inhalation Exposure; Nicotine; Smoking Water Pipes; Nicotiana; Tobacco Smoke Pollution; Water Pipe Smoking
PubMed: 31521105
DOI: 10.1186/s12199-019-0811-y -
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 -
Current Ophthalmology Reports 2021This review aims to provide an update on the clinical presentations and diagnostic findings of drug-induced retinal toxicities. (Review)
Review
PURPOSE OF REVIEW
This review aims to provide an update on the clinical presentations and diagnostic findings of drug-induced retinal toxicities.
RECENT FINDINGS
Several newly FDA-approved medications have been associated with acute retinal toxicities, including brolucizumab, MEK inhibitors, ulixertinib, and FGFR inhibitors. Additionally, as previously believed-to-be well-tolerated medications, such as pentosan sulfate sodium, anti-retroviral therapies, and certain intraoperative ocular medications, are used more frequently or for longer periods of time, associated toxic retinopathies and inflammatory reactions have been reported. Finally, advances in ocular imaging have revealed novel findings in hydroxychloroquine and tamoxifen maculopathies.
SUMMARY
Discovery of new medications, increased frequency of use, and longer-term use have led to increased reports of retinal toxicities. Advances in retinal imaging have allowed for earlier detection of subclinical changes associated with these medications, which may help prevent progression of disease. However, more research is needed to determine the point at which vision loss becomes irreversible. Risks and benefits must be assessed prior to discontinuation of the offending, but potentially lifesaving, therapy.
PubMed: 34956737
DOI: 10.1007/s40135-021-00277-x -
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