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Cells May 2024Norbormide (NRB) is a -selective toxicant, which was serendipitously discovered in 1964 and formerly marketed as an eco-friendly rodenticide that was deemed harmless to... (Review)
Review
Norbormide (NRB) is a -selective toxicant, which was serendipitously discovered in 1964 and formerly marketed as an eco-friendly rodenticide that was deemed harmless to non- species. However, due to inconsistent efficacy and the emergence of second-generation anticoagulants, its usage declined, with registration lapsing in 2003. NRBs' lethal action in rats entails irreversible vasoconstriction of peripheral arteries, likely inducing cardiac damage: however, the precise chain of events leading to fatality and the target organs involved remain elusive. This unique contractile effect is exclusive to rat arteries and is induced solely by the endo isomers of NRB, hinting at a specific receptor involvement. Understanding NRB's mechanism of action is crucial for developing species-selective toxicants as alternatives to the broad-spectrum ones currently in use. Recent research efforts have focused on elucidating its cellular mechanisms and sites of action using novel NRB derivatives. The key findings are as follows: NRB selectively opens the rat mitochondrial permeability transition pore, which may be a factor that contributes to its lethal effect; it inhibits rat vascular K channels, which potentially controls its -selective vasoconstricting activity; and it possesses intracellular binding sites in both sensitive and insensitive cells, as revealed by fluorescent derivatives. These studies have led to the development of a prodrug with enhanced pharmacokinetic and toxicological profiles, which is currently undergoing registration as a novel efficacious eco-sustainable -selective toxicant. The NRB-fluorescent derivatives also show promise as non-toxic probes for intracellular organelle labelling. This review documents in more detail these developments and their implications.
Topics: Animals; Rats; Rodenticides; Humans; Vasoconstriction; Mitochondrial Permeability Transition Pore
PubMed: 38727324
DOI: 10.3390/cells13090788 -
Toxicology Research Nov 2018The mitochondrion is an important subcellular target of environmental toxicants. With environmental stress, a series of toxic effects on mitochondria are induced, which... (Review)
Review
The mitochondrion is an important subcellular target of environmental toxicants. With environmental stress, a series of toxic effects on mitochondria are induced, which originate from the dynamic changes of mitochondrial fusion and fission, structure/membrane damage, and respiratory chain dysfunction. The toxic effects of various toxicants on mitochondrial morphology and intact membranes, and their determination of cell fate, have already been broadly studied and reported on. However, their effects on the integrity and function of the mitochondrial respiratory chain (RC) remain incompletely understood. Recently, Fan and Yu approached this topic by closely examining the mitochondrial toxicities, including the effect on the respiratory chain, induced by organic arsenical chemical 2-methoxy-4-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol and thiourea gold(i) complexes (AuTuCl). Obviously, toxicant-induced dysfunction of the respiratory chain can hinder ATP production, and may elevate ROS generation. The increased ROS can further damage mtDNA, and consequently leads to inactivation of some RC protein-encoding mtDNA, generating a vicious circle of amplifying mitochondrial damage. We hope that these studies focused on RC structure and activity will broaden our view of mitochondrial toxicology and draw forth more profound mechanistic studies on the respiratory chain toxicity of environmental toxicants and their application in risk assessment.
PubMed: 30542598
DOI: 10.1039/c8tx00207j -
Canadian Family Physician Medecin de... Jun 2014To explore the underlying causation of unexplained multimorbidity with sensitivities and to discuss the management of patients who present with this perplexing condition. (Review)
Review
OBJECTIVE
To explore the underlying causation of unexplained multimorbidity with sensitivities and to discuss the management of patients who present with this perplexing condition.
SOURCES OF INFORMATION
Medical and scientific literature was used from MEDLINE (PubMed), several books, toxicology and allergy journals, conference proceedings, government publications, and environmental health periodicals.
MAIN MESSAGE
Multimorbidity with sensitivities has become an increasingly common and confusing primary care dilemma. Escalating numbers of debilitated individuals are now presenting to family physicians and specialists with multisystem health complaints, including sensitivities and fatigue, with no obvious causation, a paucity of laboratory findings, and a lack of straightforward solutions. In the recent scientific literature, there is discussion of sensitivity-related illness, an immune-mediated disorder that frequently manifests with multisystem symptoms, commonly including sensitivities and fatigue. This condition appears to be originally caused by adverse environmental exposures and toxicant bioaccumulation-an increasingly prevalent and well-documented problem in contemporary culture.
CONCLUSION
Various toxic exposures and their bioaccumulation within the body frequently manifest as sensitivity-related illness. In clinical settings, patients with this disorder often present with otherwise unexplained multimorbidity and sensitivities. The health status of patients with this condition can be ameliorated by removing triggers (eg, scented products), optimizing biochemistry, removing further sources of toxicant exposures, and eliminating the internal dose of persistent toxicants.
Topics: Comorbidity; Disease Management; Environmental Exposure; Environmental Illness; Humans; Hypersensitivity; Prevalence; Symptom Assessment
PubMed: 24925942
DOI: No ID Found -
Toxicological Sciences : An Official... Oct 2020Studies have shown that mammalian testes, in particular the Sertoli cells, are highly susceptible to exposure of environmental toxicants, such as cadmium,... (Review)
Review
Studies have shown that mammalian testes, in particular the Sertoli cells, are highly susceptible to exposure of environmental toxicants, such as cadmium, perfluorooctanesulfonate, phthalates, 2,5-hexanedione and bisphenol A. However, important studies conducted by reproductive toxicologists and/or biologists in the past have been treated as toxicology reports per se. Yet, many of these studies provided important mechanistic insights on the toxicant-induced testis injury and reproductive dysfunction, relevant to the biology of the testis and spermatogenesis. Furthermore, recent studies have shown that findings obtained from toxicant models are exceedingly helpful tools to unravel the biology of testis function in particular spermatogenesis, including specific cellular events associated with spermatid transport to support spermiogenesis and spermiation. In this review, we critically evaluate some recent data, focusing primarily on the molecular structure and role of microtubules in cellular function, illustrating the importance of toxicant models to unravel the biology of microtubule cytoskeleton in supporting spermatogenesis, well beyond information on toxicology. These findings have opened up some potential areas of research which should be carefully evaluated in the years to come.
Topics: Animals; Cytoskeleton; Hazardous Substances; Male; Microtubules; Sertoli Cells; Spermatogenesis; Testis
PubMed: 32647867
DOI: 10.1093/toxsci/kfaa109 -
Neurotoxicology Mar 2012The exposure of the human population to environmental contaminants is recognized as a significant contributing factor for the development of Parkinson's disease (PD) and... (Review)
Review
The exposure of the human population to environmental contaminants is recognized as a significant contributing factor for the development of Parkinson's disease (PD) and other forms of parkinsonism. While pesticides have repeatedly been identified as risk factors for PD, these compounds represent only a subset of environmental toxicants that we are exposed to on a regular basis. Thus, non-pesticide contaminants, such as metals, solvents, and other organohalogen compounds have also been implicated in the clinical and pathological manifestations of these movement disorders and it is these non-pesticide compounds that are the subject of this review. As toxic exposures to these classes of compounds can result in a spectrum of PD or PD-related disorders, it is imperative to appreciate shared clinico-pathological characteristics or mechanisms of action of these compounds in order to further delineate the resultant disorders as well as identify improved preventive strategies or therapeutic interventions.
Topics: Environmental Exposure; Hazardous Substances; Humans; Parkinson Disease; Risk Factors
PubMed: 22309908
DOI: 10.1016/j.neuro.2012.01.010 -
Toxics May 2020Biomarkers of environmental toxicants are measures of exposures and effects, some of which can serve to assess disease risk and interindividual susceptibilities.[...].
Biomarkers of environmental toxicants are measures of exposures and effects, some of which can serve to assess disease risk and interindividual susceptibilities.[...].
PubMed: 32456001
DOI: 10.3390/toxics8020037 -
Cellular & Molecular Biology Letters 2019Common environmental pollutants and drugs encountered in everyday life can cause toxic damage to the body through oxidative stress, inflammatory stimulation, induction... (Review)
Review
Common environmental pollutants and drugs encountered in everyday life can cause toxic damage to the body through oxidative stress, inflammatory stimulation, induction of apoptosis, and inhibition of energy metabolism. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, is a member of the evolutionarily highly conserved Sir2 (silent information regulator 2) superprotein family, which is located in the nucleus and cytoplasm. It can deacetylate protein substrates in various signal transduction pathways to regulate gene expression, cell apoptosis and senescence, participate in the process of neuroprotection, energy metabolism, inflammation and the oxidative stress response in living organisms, and plays an important role in toxic damage caused by toxicants and in the process of SIRT1 activator/inhibitor antagonized toxic damage. This review summarizes the role that SIRT1 plays in toxic damage caused by toxicants via its interactions with protein substrates in certain signaling pathways.
Topics: Animals; Humans; Models, Biological; Signal Transduction; Sirtuin 1; Toxins, Biological
PubMed: 31164908
DOI: 10.1186/s11658-019-0158-9 -
Environmental Science and Pollution... May 2014The nutritional profile of an individual can influence the toxicity of persistent environmental toxicants. Polychlorinated biphenyls (PCBs), prevalent environmental... (Review)
Review
The nutritional profile of an individual can influence the toxicity of persistent environmental toxicants. Polychlorinated biphenyls (PCBs), prevalent environmental pollutants, are highly lipid-soluble toxic compounds that biomagnify through trophic levels and pose cancer, neurocognitive, and atherosclerotic risk to human populations. There is a growing body of knowledge that PCBs can initiate inflammatory responses in vivo, and this inflammation can be either exacerbated or ameliorated by nutrition. Data indicate that diets high in certain dietary lipids such as omega-6 fatty acids can worsen PCB-induced vascular toxicity while diets enriched with bioactive food components such as polyphenols and omega-3 polyunsaturated fatty acids can improve the toxicant-induced inflammation. There is evidence that bioactive nutrients protect through multiple cell signaling pathways, but we have shown that lipid raft caveolae and the antioxidant defense controller nuclear factor (erythroid-derived 2)-like 2 (Nrf2) both play a predominant role in nutritional modulation of PCB-induced vascular toxicity. Interestingly, there appears to be an intimate cross-talk between caveolae-related proteins and cellular Nrf2, and focusing on the use of specific bioactive food components that simultaneously alter both pathways may produce a more effective and efficient cytoprotective response to toxicant exposure. The use of nutrition as a protective tool is an economically beneficial means to address the toxicity of persistent environmental toxicants and may become a sensible means to protect human populations from PCB-induced vascular inflammation and associated chronic diseases.
Topics: Diet; Dietary Fats; Environmental Exposure; Environmental Pollutants; Humans; Nutritional Status; Polychlorinated Biphenyls; Signal Transduction; Vasculitis
PubMed: 23417440
DOI: 10.1007/s11356-013-1549-5 -
Toxics Jan 2020Reproductive dysfunction is often characterized by malfunction of the reproductive tissues, which may lead to disruption of the synergistic rhythm that should bring... (Review)
Review
Reproductive dysfunction is often characterized by malfunction of the reproductive tissues, which may lead to disruption of the synergistic rhythm that should bring about a progression of sexual events and the conception of new life. This may therefore result in the sexual dysfunction and infertility that can be seen in couples having prolonged biological difficulty in reproducing their offspring after having unrestricted sexual intercourse for at least twelve months. Several factors have been implicated in the cause and progression of reproductive dysfunction, including poor nutrition, drug side effects, disease states, and toxicant ingestion. A well-known food additive that has been found to be potent at initiating reproductive anomalies in males is monosodium glutamate (MSG). This regular flavor enhancer is widely used as a taste enhancer in several diets. The different mechanisms by which it may induce reproductive dysfunctions include spermatogenic alteration resulting in a low sperm count, high sperm abnormality, reduced live sperm and decreased sperm pH, oxidative damage (increased lipid peroxidation and reduced antioxidant enzyme activities), histological alteration (blood hemorrhage, distorted germ and Sertoli cells), as well as gonadotropin imbalance (reduced testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations). Therefore, this review discusses various established mechanisms through which MSG may induce reproductive dysfunction and the treatment strategies to ameliorate its toxic effects.
PubMed: 31979139
DOI: 10.3390/toxics8010007 -
International Journal of Environmental... Apr 2019Environmental factors are recognized as risk factors of thyroid cancer in humans. Exposure to radiation, both from nuclear weapon or fallout or medical radiation, and to... (Review)
Review
Environmental factors are recognized as risk factors of thyroid cancer in humans. Exposure to radiation, both from nuclear weapon or fallout or medical radiation, and to some organic and inorganic chemical toxicants represent a worldwide public health issue for their proven carcinogenicity. Halogenated compounds, such as organochlorines and pesticides, are able to disrupt thyroid function. Polychlorinated biphenyls and their metabolites and polybrominated diethyl ethers bind to thyroid, transport proteins, replace thyroxin, and disrupt thyroid function as phthalates and bisphenolates do, highly mimicking thyroid hormones. A better knowledge of environmental risks represents a very important tool for cancer prevention through true risks prevention and management. This approach is very important because of the epigenetic origin's theory of cancer. Therefore, the aim of this review was study the association between environmental agents and thyroid cancer promotion.
Topics: Carcinogens; Environmental Pollutants; Humans; Risk Factors; Thyroid Gland
PubMed: 30986998
DOI: 10.3390/ijerph16071185