Metals neurotoxicity

Walsh TJ, DeHaven DL. 1988. Neurotoxicity of the alkyltins. In Bondy SC, Prasad KN, eds. Metal neurotoxicity. Boca Raton, FL CRC Press, 87-107. 

Carpenter DO. 1994. The public health significance of metal neurotoxicity. Cell Mol Neurobiol 14 591-597. 

See also Metals Neurotoxicity Pollution, Soil Pollution, Water Sister Chromatid Exchanges Skin. 

Yasui M, Strong MJ, Ota K, and Verity MA (1997) Mineral and Metal Neurotoxicity. Boca Raton, FL GRG Press. 

See also Metals Neurotoxicity Organotins Poiiution, Water. 

See also Analytical Toxicology Behavioral Toxicology Metals Neurotoxicity Ototoxicity Organophosphates Petroleum Distillates Psychological Indices of Toxicity. 

Cooper GP, Fox DA, Howell WE, et al. 1980. Visual evoked responses in rats exposed to heavy metals. In MeriganWH, Weiss B, eds. Neurotoxicity of the visual system. New York, NY Raven Press, 203-218. 

Knowledge of the intracellular thermodynamics and kinetics of metal metabolism may become useful in the design of compounds that alter intracellular metal ion availability. This in turn may be useful in controlling such biological phenomena as cancer cell proliferation, disorders of metal metabolism, and metal-induced neurotoxicity. 

Reasons for chopping clinical candidates at any stage of the drug approval process included (1) stability, formulation, or other pharmaceutical development issues, (2) renal toxicity or neurotoxicity, and (3) insufficient advantage over current chugs. Since 1997, the NCI has also operated a screen for compounds active against the cytotoxic effects of HIV in CEM cells. Of 80,000 compounds tested, 4050 (or about 5%) were active. Of the compounds tested, 2291 have included metals. Of those, 136 (about 6%) were active, and two became clinical candidates. Both were chopped due to toxicity problems. One clinical candidate was a polyoxometallate, and therefore about 80 other similar molecules were tested. These were found to be strongly active in vitro, but too toxic in animal models in vivo. If a way around the toxicity problem can be found, interest in these... 

The results of the investigation of 58 adult persons who live on industry territory of North Crimea and 60 male teenagers at age 15 years and 84 children (2-14 years) in the Simferopol city showed that the children are more sensitive to the relatively low level of heavy metal concentrations than the adult (Evstafyeva et al., 2002). It is known that many toxic metals have neurotoxic effects (Arezzo et al., 1985). It was also shown that the effects of central and autonomous nervous systems of different... 

Bachmann MO, De Beer Z, Myers JE. 1993. -Hexane neurotoxicity in metal can manufacturing workers. Occup Med 43 149-154. 

Synaptotagmins are yet another family of Ca2+-binding proteins, localized on the membranes of synaptic vesicles, where they seem to be involved in the release of neurotransmitters. While the mechanism by which they are involved in Ca2+-mediated synaptic transmission is unclear, it seems likely that the neurotoxicity of heavy metals such as Pb is due to a higher affinity of synaptotagmins for Pb2+ than for Ca2+. 

The RfDs and TDIs are often used to establish regulatory standards. Such standards usually specify a limit on the allowable concentration of a chemical in an environmental medium. The process is not difficult to understand. The RfD and its related estimates of population thresholds is a dose, typically expressed in mg/(kg b.w. day), that is considered to be without significant risk to human populations exposed daily, for a lifetime. Consider mercury, a metal for which an RfD of 0.0003 mg/(kg b.w. day) has been established by the EPA, based on certain forms of kidney toxicity observed in rats (Table 8.4). These are not the only toxic effects of mercury, but they are the ones seen at the lowest doses. Note also that we are dealing with inorganic mercury, not the methylated form that is neurotoxic. 

Mercury Metal - persistent - bioaccumulates - contaminates many species of fish. Widely used in industrial processes. Causes developmental neurotoxicity -children most susceptible... 

Neurotoxicity. No studies were located regarding the neurological effects of thorium in humans or animals following exposure by any route. Other metals, such as lead, however, have been shown to have more severe neurological effects on children than adults therefore, it is possible that children may be more susceptible than adults to the effects of thorium. Studies on the neurological effects of thorium, both histopathological and effects on behavior by all relevant routes of exposure in animals, may determine the potential neurological effects in humans. 

Reactive oxygen species production is largely catalyzed by transition metals (especially copper and iron), and oxidative stress plays a critical role in AD pathogenesis. In one study, the association of metal levels and Ap toxicity was demonstrated by (i) the effect on cell viability by metal alone and in the combination with APP and Ap, (ii) Ap-induced neurotoxicity relevant to oxidative stress indicated by ROS production, and (iii) APPsw cells expressed APP and generated Ap, so that Ap Cu2+ and APP Cu2+ can catalyze more ROS generation than APP cells that only expressed APP. 

Nicotine shows protective effects against Ap-induced neurotoxicity in vivo and in vitro. Although nicotine acts on nAChRs, it also contains metal chelating abilities. It has been shown that maternal nicotine exposure resulted in a reduction of the copper content in the neonatal lung. In addition, evidence has been accumulated that nicotine might chelate metals. Indeed, nicotine reduces the levels of copper and zinc in senile plaques and neuropil, counteracting the undesirable metal accumulation. 

Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI. 1999b. Cu(II) potentiation of Alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 274 37111-37116. 

Zhang J, Liu Q, Chen Q, Liu NQ, Li FL, Lu ZB, Qin C, Zhu H, Huang YY, He W, Zhao BL. 2006. Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis. FASEB J 20 1212-1214. 

Uptake of Toxic Divalent Metal Ions in Neurotoxicity Induced by Kainate... 

Neurobehavioral assessment of workers in occupations or industries with chronic exposure to tin and other heavy metals with known neurotoxic properties. 

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