Nerve Membrane Ion Channels as the Target Site of Environmental Toxicants

Narahashi, Toshio

doi:10.2307/3430410

Cited by 2 publications

(2 citation statements)

References 8 publications

(12 reference statements)

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“…These results are not surprising with metals. Synapses are a major site of mercury neurotoxicity (136)(137)(138). Presynaptically, mercury blocks sodium and calcium channels (139).…”

Section: Anti-nf-68mentioning

confidence: 99%

Neuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms.

El-Fawal

Waterman

Feo

et al. 1999

Environ Health Perspect

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The interactions between the nervous and immune systems have been recognized in the development of neurodegenerative disease. This can be exploited through detection of the immune response to autoantigens in assessing the neurotoxicity of environmental chemicals. To test this hypothesis, the following questions were addressed. a) Are autoantibodies to nervous system (NS) antigens detected in populations exposed to environmental or occupational chemicals? In sera of male workers exposed to lead or mercury, autoantibodies, primarily IgG, to neuronal cytoskeletal proteins, neurofilaments (NFs), and myelin basic protein (MBP) were prevalent. These findings were confirmed in mice and rats exposed to either metal. b) Do autoantibodies to NS antigens relate to indices of exposure? In humans exposed to either metal, and similarly in exposed rats, titers of IgG against NFs and MBP significantly correlated with blood lead or urinary mercury, the typical indices of exposure. c) Do autoantibodies correlate with sensorimotor deficits? In workers exposed to lead or mercury, a significant correlation was observed between IgG titers and subclinical deficits. Doses of metals used in rat exposures were subclinical, suggesting that autoantibodies may be predictive of neurotoxicity. d) Is the detection indicative of nervous system pathology? In rats exposed to metals, histopathology indicated central nervous system (CNS) and peripheral nervous system (PNS) damage. In addition there was evidence of astrogliosis, which is indicative of neuronal damage in the CNS, and the presence of IgG concentrated along the blood-brain barrier, as indicated by immunostaining for antibodies. e) Are immune responses to NS antigens pathogenic? Immunoglobulin fractions from rat and human sera interfered with neuromuscular function. These studies suggest that the detection of autoantibodies to NS-specific antigens may be used to monitor the development of neurotoxicity to environmental chemicals and that immune mechanisms may be involved in the progression of neurodegeneration.ImagesFigure 5Figure 6Figure 7

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“…These results are not surprising with metals. Synapses are a major site of mercury neurotoxicity (136)(137)(138). Presynaptically, mercury blocks sodium and calcium channels (139).…”

Section: Anti-nf-68mentioning

confidence: 99%

Neuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms.

El-Fawal

Waterman

Feo

et al. 1999

Environ Health Perspect

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“…As for pyrethroids, DDT slows the rate of activation of voltage-gated sodium channels and inhibits inactivation causing long sodium currents in mammals and insects. Hence, like pyrethroids, DDT compounds disrupt nerve transmission leading to symptoms as those described above (Narahashi, 1987(Narahashi, , 1993.…”

Section: Pesticides (Pyrethroids and Organochlorine Insecticides)mentioning

confidence: 99%

Ion channels in toxicology

Restrepo-Angulo

Vizcaya-Ruiz

Camacho

2010

J of Applied Toxicology

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Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases.

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Nerve Membrane Ion Channels as the Target Site of Environmental Toxicants

Cited by 2 publications

References 8 publications

Neuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms.

Neuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms.

Ion channels in toxicology

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