Neurotoxicity of Metal Mixtures Andrade, V M; Aschner, M; Marreilha Dos Santos, A P
Advances in neurobiology,
2017, Volume:
18
Journal Article
Peer reviewed
Metals are the oldest toxins known to humans. Metals differ from other toxic substances in that they are neither created nor destroyed by humans (Casarett and Doull's, Toxicology: the basic science ...of poisons, 8th edn. McGraw-Hill, London, 2013). Metals are of great importance in our daily life and their frequent use makes their omnipresence and a constant source of human exposure. Metals such as arsenic As, lead Pb, mercury Hg, aluminum Al and cadmium Cd do not have any specific role in an organism and can be toxic even at low levels. The Substance Priority List of Agency for Toxic Substances and Disease Registry (ATSDR) ranked substances based on a combination of their frequency, toxicity, and potential for human exposure. In this list, As, Pb, Hg, and Cd occupy the first, second, third, and seventh positions, respectively (ATSDR, Priority list of hazardous substances. U.S. Department of Health and Human Services, Public Health Service, Atlanta, 2016). Besides existing individually, these metals are also (or mainly) found as mixtures in various parts of the ecosystem (Cobbina SJ, Chen Y, Zhou Z, Wub X, Feng W, Wang W, Mao G, Xu H, Zhang Z, Wua X, Yang L, Chemosphere 132:79-86, 2015). Interactions among components of a mixture may change toxicokinetics and toxicodynamics (Spurgeon DJ, Jones OAH, Dorne J-L, Svendsen C, Swain S, Stürzenbaum SR, Sci Total Environ 408:3725-3734, 2010) and may result in greater (synergistic) toxicity (Lister LJ, Svendsen C, Wright J, Hooper HL, Spurgeon DJ, Environ Int 37:663-670, 2011). This is particularly worrisome when the components of the mixture individually attack the same organs. On the other hand, metals such as manganese Mn, iron Fe, copper Cu, and zinc Zn are essential metals, and their presence in the body below or above homeostatic levels can also lead to disease states (Annangi B, Bonassi S, Marcos R, Hernández A, Mutat Res 770(Pt A):140-161, 2016). Pb, As, Cd, and Hg can induce Fe, Cu, and Zn dyshomeostasis, potentially triggering neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Additionally, changes in heme synthesis have been associated with neurodegeneration, supported by evidence that a decline in heme levels might explain the age-associated loss of Fe homeostasis (Atamna H, Killile DK, Killile NB, Ames BN, Proc Natl Acad Sci U S A 99(23):14807-14812, 2002).The sources, disposition, transport to the brain, mechanisms of toxicity, and effects in the central nervous system (CNS) and in the hematopoietic system of each one of these metals will be described. More detailed information on Pb, Mn, Al, Hg, Cu, and Zn is available in other chapters. A major focus of the chapter will be on Pb toxicity and its interaction with other metals.
Abstract Background Metal poisonings through a mucocutaneous route are reported rarely in the literature. Methods We report 2 cases of heavy metal intoxication from inappropriate use of Chinese ...mineral medicines confirmed by toxicologic investigations. Results A 51-year-old man developed perianal gangrene and a high fever after a 2-week anal use of hong-dan herbal mixtures for anal fistula. He presented gastrointestinal and constitutional symptoms, followed by skin rash, anemia, hair loss, peripheral neuropathy, and muscle atrophy. Elevated urine arsenic and mercury confirmed the heavy metal poisonings. The hong-dan mixture contained lead tetraoxide, arsenic, and mercury. He was treated with 2,3-dimercapto-1-propanesulfonic acid, with partial improvement, but peripheral neuropathy persists 4 years later. A 75-year-old man developed anorexia, weight loss, headache, dizziness, nausea, vomiting, constipation, weakness, and anemia after a 3-month use of an herbal patch for chronic leg ulcer. His blood lead concentration was 226 μg/dL, and the lead content of the herbal patch was 517 mg/g. Chelation with ethylene diamine tetraacetic acid and dimercaptosuccinic acid was followed by clinical recovery. Conclusion These cases documented serious systemic poisoning after the short-term use of traditional Chinese medicines containing heavy metals in damaged or infected tissue.
Dinoflagellates are not only important marine primary producers and grazers, but also the major causative agents of harmful algal blooms. It has been reported that many dinoflagellate species can ...produce various natural toxins. These toxins can be extremely toxic and many of them are effective at far lower dosages than conventional chemical agents. Consumption of seafood contaminated by algal toxins results in various seafood poisoning syndromes: paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP), diarrheic shellfish poisoning (DSP), ciguatera fish poisoning (CFP) and azaspiracid shellfish poisoning (ASP). Most of these poisonings are caused by neurotoxins which present themselves with highly specific effects on the nervous system of animals, including humans, by interfering with nerve impulse transmission. Neurotoxins are a varied group of compounds, both chemically and pharmacologically. They vary in both chemical structure and mechanism of action, and produce very distinct biological effects, which provides a potential application of these toxins in pharmacology and toxicology. This review summarizes the origin, structure and clinical symptoms of PSP, NSP, CFP, AZP, yessotoxin and palytoxin produced by marine dinoflagellates, as well as their molecular mechanisms of action on voltage-gated ion channels.
This review provides an update on recently published literature on the rise of illicit fentanyls, risks for overdose, combinations with other substances, e.g. stimulants, consequences, and treatment.
...Overdose due to illicit synthetic opioids (e.g. fentanyl and fentanyl analogs) continues to rise in the US both preceding and during the COVID-19 pandemic. Fentanyl-related overdose is rising in new geographic areas e.g. the western USA. Stimulant-related overdose is also increasing nationwide driven by methamphetamine and cocaine. Polysubstance use, e.g. the use of a stimulant along with an opioid is driving stimulant-related overdose. Other medical consequences of injection drug use are rising including HIV and hepatitis C infections. Medication approaches to treating opioid use disorder remain the standard of care and there are new promising pharmacological approaches to treating methamphetamine use disorder.
A 'fourth wave' of high mortality involving methamphetamine and cocaine use has been gathering force in the USA. Availability and use of illicit fentanyls are still the major drivers of overdose deaths and the current rise in stimulant-related deaths appears entwined with the ongoing opioid epidemic.
Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex ...array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties.
The term organophosphate (OP) refers to a diverse group of chemicals that are found in hundreds of products worldwide. As pesticides, their most common use, OPs are clearly beneficial for ...agricultural productivity and the control of deadly vector-borne illnesses. However, as a consequence of their widespread use, OPs are now among the most common synthetic chemicals detected in the environment as well as in animal and human tissues. This is an increasing environmental concern because many OPs are highly toxic and both accidental and intentional exposures to OPs resulting in deleterious health effects have been documented for decades. Some of these deleterious health effects include a variety of long-term neurological and psychiatric disturbances including impairments in attention, memory, and other domains of cognition. Moreover, some chronic illnesses that manifest these symptoms such as Gulf War Illness and Aerotoxic Syndrome have (at least in part) been attributed to OP exposure. In addition to acute acetylcholinesterase inhibition, OPs may affect a number of additional targets that lead to oxidative stress, axonal transport deficits, neuroinflammation, and autoimmunity. Some of these targets could be exploited for therapeutic purposes. The purpose of this review is thus to: 1) describe the important uses of organophosphate (OP)-based compounds worldwide, 2) provide an overview of the various risks and toxicology associated with OP exposure, particularly long-term neurologic and psychiatric symptoms, 3) discuss mechanisms of OP toxicity beyond cholinesterase inhibition, 4) review potential therapeutic strategies to reverse the acute toxicity and long term deleterious effects of OPs.
Lead wars Markowitz, Gerald; Rosner, David
2013., 20130306, 2013, 2013-04-30, Volume:
24
eBook
In this incisive examination of lead poisoning during the past half century, Gerald Markowitz and David Rosner focus on one of the most contentious and bitter battles in the history of public health. ...Lead Wars details how the nature of the epidemic has changed and highlights the dilemmas public health agencies face today in terms of prevention strategies and chronic illness linked to low levels of toxic exposure. The authors use the opinion by Maryland's Court of Appeals—which considered whether researchers at Johns Hopkins University's prestigious Kennedy Krieger Institute (KKI) engaged in unethical research on 108 African-American children—as a springboard to ask fundamental questions about the practice and future of public health. Lead Wars chronicles the obstacles faced by public health workers in the conservative, pro-business, anti-regulatory climate that took off in the Reagan years and that stymied efforts to eliminate lead from the environments and the bodies of American children.
Scholarship on women and homicide has focused increasingly on the ways in which race, class, ethnicity, and sexual identity intersect to produce patterns of severity and leniency toward women accused ...of murder. However, prosecutions of individuals rarely hook neatly into such matrices. This article uses an alleged instance of husband poisoning in early Federation New South Wales to illustrate the capacity of case studies to illuminate the contingencies of capital justice. Far from an instance of women's lethal violence springing from male abuse, or a straightforward example of the patriarchal legal system at work, Jane Hetherington's conviction was a likely miscarriage of justice.
The aim of this study has been to assess the characteristics of acute poisoning deaths in Poland over a period of time 2009-2013.
The analysis was based on the data obtained from the patient records ...stored in toxicology departments in 6 cities - Łódź, Kraków, Sosnowiec, Gdańsk, Wrocław and Poznań. Toxicological analyses were routinely performed in blood and/or urine. Major toxic substances were classified to one of the following categories: pharmaceuticals, alcohol group poisonings (ethanol and other alcohols), gases, solvents, drugs of abuse, pesticides, metals, mushrooms, others. Cases were analyzed according to the following criteria: year, age and gender of analyzed patients, toxic substance category and type of poisoning. The recorded fatal poisonings were classified according to the International Classification of Diseases.
The record of 261 deaths were retrospectively reviewed. There were 187 males (71.64%) and 74 females (28.36%) and the male to female ratio was 2.52. Alcohol group poisonings were more frequently responsible for deaths in men compared to all poisonings, 91.1% vs. 71.6%, respectively (p < 0.05), and pharmaceutical agents were more frequently responsible for deaths in women, 47.4% vs. 28.4%, (p < 0.05). Methanol was the most common agent in the alcohol group poisonings, accounting for 43.75% (N = 49), followed by ethylene glycol, 39.29% (N = 44), and ethanol, 16.96% (N = 19).
Epidemiological profile data from investigation of poisoning deaths in Poland may be very useful for the development of preventive programs. Int J Occup Med Environ Health 2017;30(6):897-908.
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