Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Philbert, M. A.
Right arrow Articles by Reuhl, K. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Philbert, M. A.
Right arrow Articles by Reuhl, K. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Mechanisms of Injury in the Central Nervous System

Martin A. Philbert

Neurotoxicology and Experimental Neuropathology Labs, Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan 48109-2029

Melvin L. Billingsley

Department of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania 17033

Kenneth R. Reuhl

Neurotoxicology Laboratories, College of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, New Jersey 08854

Neurotoxicants with similar structural features or common mechanisms of chemical action frequently produce widely divergent neuropathologic outcomes. Methylmercury (MeHg) produces marked cerebellar dysmorphogenesis during critical periods of development. The pathologic picture is characterized by complete architectural disruption of neuronal elements within the cerebellum. MeHg binds strongly to protein and soluble sulphydryl groups. Binding to microtubular -SH groups results in catastrophic depolymerization of immature tyrosinated microtubules. However, more mature acetylated microtubules are resistant to MeHg-induced depolymerization. In contrast to MeHg, the structurally similar organotin trimethyltin (TMT) elicits specific apoptotic destruction of pyramidal neurons in the CA3 region of the hippocampus and in other limbic structures. Expression of the phylogenetically conserved protein stannin is required for development of TMT-induced lesions. Inhibition of expression using antisense oligonucleotides against stannin protects neurons from the effects of TMT, suggesting that this protein is required for expression of neurotoxicity. However, expression of stannin alone is insufficient for induction of apoptotic pathways in neuronal populations. The aromatic nitrocompound 1,3-dinitrobenzene (DNB) has 2 independent nitro groups that can redox cycle in the presence of molecular oxygen. Despite its ability to deplete neural glutathione stores, DNB produces edematous gliovascular lesions in the brain stem of rats. Glial cells are susceptible despite high concentrations of reduced glutathione compared with neuronal somata in the central nervous system (CNS). The severity of lesions produced by DNB is modulated by the activity of neurons in the affected pathways. The inherent discrepancy between susceptibility of neuronal and glial cell populations is likely mediated by differential control of the mitochondrial permeability transition in astrocytes and neurons. Lessons learned in the mechanistic investigation of neurotoxicants suggest caution in the evaluation and interpretation of structure-activity relationships, eg, TMT, MeHg, and DNB all induce oxidative stress, whereas TMT and triethyltin produce neuronal damage and myelin edema, respectively. The precise CNS molecular targets of cell-specific lipophilic neurotoxicants remain to be determined.

Key Words: Central nervous system • 1,3-dinitrobenzene • mechanisms • methylmercury • neurotoxicity • organometals • stannin • trimethyltin

References

  • Ali SF, Lebel CP, Bondy SC (1992). Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13: 637-648.[Web of Science][Medline] [Order article via Infotrieve]
  • Ally A., Buist R., Mills P., Reuh K. ( 1993). Effects of methylmercury and trimethyltin on cardiac, platelet, and aorta eicosanoid biosynthesis and platelet serotonin release. Pharmacol Biochem Behav 44: 555-563.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Amin-Zaki L., Elhassani SB, Majeed MA, Clarkson TW, Doherty RA, Greenwood MR (1980). Methylmercury poisoning in mothers and their suckling infants. Dev Toxicol Environ Sci 8: 75-78.[Medline] [Order article via Infotrieve]
  • Amin-Zaki L., Elhassani S., Majeed MA, Clarkson TW, Doherty RA, Greenwood MR, Giovanoli-Jakubczak T. ( 1976). Perinatal methylmercury poisoning in Iraq. Am J Dis Child 130: 1070-1076.[Abstract/Free Full Text]
  • Amin-Zaki L., Majeed MA, Clarkson TW, Greenwood MR (1978). Methylmercury poisoning in Iraqi children: Clinical observations over two years. Br Med J 1: 613-616.[Abstract/Free Full Text]
  • Amin-Zaki L., Majeed MA, Elhassani SB, Clarkson TW, Greenwood MR, Doherty RA (1979). Prenatal methylmercury poisoning. Clinical observations over five years. Am J Dis Child 133: 172-177.[Abstract/Free Full Text]
  • Amin-Zaki L., Majeed MA, Greenwood MR, Elhassani SB, Clarkson TW, Doherty RA (1981). Methylmercury poisoning in the Iraqi suckling infant: A longitudinal study over five years. J Appl Toxicol 1: 210-214.[Medline] [Order article via Infotrieve]
  • Anundi I., Kaufman FC, teKoppele JM, Yamanaka H., Whittaker M., Popp JA, Thurman RJ (1989). Adenine nucleotides and carbohydrates in cell populations of hepatic nodules with normal and compromised microcirculation. Cancer Res 49: 3282-3286.[Abstract/Free Full Text]
  • Aschner M., Aschner JL (1992). Cellular and molecular effects of trimethyltin and triethyltin: Relevance to organotin neurotoxicity. Neurosc Behav Rev 16: 427-435.
  • Atchison WD (1986). Extracellular calcium-dependent and -independent effects of methylmercury on spontaneous and potassium-evoked release of acetylcholine at the neuromuscular junction. J Pharmacol Exp Ther 237: 672-680.[Abstract/Free Full Text]
  • Bagley PR, Tucker SP, Nolan C., Lindsay JP, Davies A., Baldwin SA, Cramer JE, Cunningham VJ (1989). Anatomical mapping of glucose transporter protein and pyruvate dehydrogenase in rat brain: An immunogold study. Brain Res 499: 214-224.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bailey E., Peal JA, Philbert M. (1988). Determination of 1,3-dinitrobenzene and its metabolites in rat blood by capillary gas chromatography with electron-capture detection. J Chromatogr 425: 187-192.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bakir F., Damluji SF, Amin-Zaki L., Murtadha M., Khalidi A., al-Rawi NY, Tikriti S., Dahahir HI, Clarkson TW, Smith JC, Doherty RA (1973). Methylmercury poisoning in Iraq. Science 181: 230-241.[Free Full Text]
  • Balaban CD, O'Callaghan JP, Billingsley ML (1988). Trimethyltin-induced neuronal damage in the rat brain: Comparative studies using silver degeneration stains, immunocytochemistry and immunoassay for neuronotypic and gliotypic proteins. Neuroscience 26: 337-361.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Berlin M. (1979). Mercury. In: Handbook on the Toxicology of Metals, Freiberg L (ed). Elsevier, North-Holland, Amsterdam, pp 503-529.
  • Bollweg G., Ballaban Cox HJ, Berra B., Sparber SB (1995). Potential efficacy and toxicity of GM1 ganglioside against trimethyltin-induced brain lesions in rats: Comparison with protracted food restriction. Neurotoxicology 16: 239-256.[Web of Science][Medline] [Order article via Infotrieve]
  • Bouldin TW, Goines ND, Bagnell CR, Krigman MR (1981). Pathogenesis of trimethyltin neuronal toxicity. Am J Pathol 104: 237-249.[Abstract]
  • Boyer IJ (1989). Toxicity of dibutyltin, tributyltin and other organotin compounds to humans and to experimental animals. Toxicology 55: 253-298.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Brodie AE, Reed DJ ( 1992). Glutathione disulfide reduction in tumor mitochondria after t-butyl hydroperoide treatment. Chem Biol Interact 84: 125-132.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Brown AW, Aldridge WN, Street BW, Verschoyle RD (1979). The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat. Am J Pathol 97: 59-82.[Abstract]
  • Brown AW, Cavanagh JB, Verschoyle RD, Gysbers MF, Jones HB, Aldridge WN (1984). Evolution of the intracellular changes in neurons caused by trimethyltin. Neuropathol App Neurobiol 10: 267-283.
  • Brubaker PE, Klein R., Herman SP, Lucier GW, Alexander LT, Long MD (1973). DNA, RNA and protein synthesis in brain, liver and kidneys of assymptomatic methylmercury treated rats. Exp Mol Pathol 18: 263-280.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Calingasan NY, Baker H., Sheu KP, Gibson GE (1994). Selective enrichment of cholinergic neurons with the alpha-ketoglutarate dehydrogenase complex in rat brain. Neurosci Lett 168: 209-212.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cavanagh JB (1988). Long term persistence of mercury in the brain. Br J Indus Med 45: 649-651.[Web of Science][Medline] [Order article via Infotrieve]
  • Cavanagh JB, Chen FC (1971). Amino acid incorporation in protein during the "silent phase" before organo-mercury and p-bromophenylacetylurea neuropathy in the rat. Acta Neuropathol 19: 216-224.[CrossRef][Medline] [Order article via Infotrieve]
  • Cavanagh JB, Nolan CC (1993). The neurotoxicity of alpha-chlorohydrin in rats and mice: II. Lesion topography and factors in selective vulnerability in acute energy deprivation syndromes. Neuropathol Appl Neurobiol 19: 471-479.[Web of Science][Medline] [Order article via Infotrieve]
  • Cavanagh JB, Nolan CC, Seville MP (1993). The neurotoxicity of alpha-chlorohydrin in rats and mice: I. Evolution of the cellular changes. Neuropathol Appl Neurobiol 19: 240-252.[Web of Science][Medline] [Order article via Infotrieve]
  • Chacon E., Reece JM, Nieminen AL, Zahrebelski G., Herman B., Lemasters JJ (1994). Distribution of electrical potential, pH, free Ca2+, and volume inside cultured adult rabbit cardiac myocytes during chemical hypoxia: A multiparameter digitized confocal microscopic study. Biophys J 66: 942-952.[Web of Science][Medline] [Order article via Infotrieve]
  • Chang LW (1977). Neurotoxic effects of mercury—A review. Environ Res 13: 329-373.
  • Chang LW (1980). Neurotoxic effects of mercury. In: Experimental and Clinical Neurotoxicology, Spencer PS, Schaumberg HH (eds). Williams and Wilkins, Baltimore, Maryland, pp 508-526.
  • Chang LW (1982). Pathogenetic mechanisms of the neurotoxicity of methylmercury. In: Mechanisms of Neurotoxic Substances, Prasad KN, Vernadakis A (eds). Raven Press, New York, pp 51-66.
  • Chang LW (1984). Developmental toxicology of methylmercury. In: Toxicology and the Newborn, Kacew S, Reasor NJ (eds). Elsevier, Amsterdam, pp 175-197.
  • Chang LW (1990). The neurotoxicology and pathology of organomercury, organolead, and organotin. J Toxicol Sci 15 (suppl 4): 125-151.[Medline] [Order article via Infotrieve]
  • Chang LW, Desnoyers PA, Hartmann HA (1973). Quantitative cytochemical studies of RNA in experimental mercury poisoning. II. Changes in the base composition and ratios. Acta Neuropathol 23: 77-83.[CrossRef][Medline] [Order article via Infotrieve]
  • Chang LW, Gilbert M., Sprecher J. (1978). Modification of methylmercury neurotoxicity by vitamin E. Environ Res 17: 356-366.[Medline] [Order article via Infotrieve]
  • Chang LW, Hartmann HA (1972). Electron microscopic histochemical study on the localization and distribution of mercury in the nervous system after mercury intoxication. Exp Neurol 35: 122-137.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Chang LW, Martin AH, Hartmann HA (1972). Quantitative autoradiographic study on the RNA synthesis in the neurons after mercury intoxication. Exp Neurol 37: 62-67.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Chang LW, Reuhl KR (1983). Mercury effects on human and animal health. In: Trace Elements and Health, Rose J (ed). IPC Science Technology Press, London, pp 132-149.
  • Chang LW, Reuhl KR, Lee GW ( 1977). Degenerative changes in the developing nervous system as a result of in utero exposure to methylmercury. Environ Res 14: 414-423.[Medline] [Order article via Infotrieve]
  • Chang LW, Reuhl KR, Spyker JM (1977). Ultrastructural study of the latent effects of methyl mercury on the nervous system after prenatal exposure. Environ Res 13: 171-185.[Medline] [Order article via Infotrieve]
  • Chang LW, Verity MA (1995). Mercury neurotoxicity: Effects and mechanisms. In: Handbook of Neurotoxicology, Chang LW, Dyer RS (eds). Marcel Dekker, New York, pp 31-59.
  • Chang LW, Wade PR, Pounds JG, Reuhl KR (1980). Prenatal and neonatal toxicology and pathology of heavy metals. Adv Pharmacol Chemother 17: 195-231.[Medline] [Order article via Infotrieve]
  • Cheung MK, Verity MA (1985). Experimental methyl mercury neurotoxicity: Locus of mercurial inhibition of brain protein synthesis in vivo and in vitro. J Neurochem 44: 1799-808.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Clark H., Kopelman K., Athey B., Ade A., Meixner W., Hill D., Lightle R., Hoyer M., Philbert MA (1998). Subcellular optochemical nanobiosensors: Probes encpasulated by biologically-localized embedding (PEBBLEs). Sensors Actuators B 51: 12-16.[CrossRef]
  • Clarkson TW, Marsh DO (1982). Mercury toxicity in man. In: Clinical, Biochemical and Nutritional Aspects of Trace Elements, Prasad AS (ed). Alan R Liss, New York, pp 549-568.
  • Clerici WJ (1996). Effects of superoxide dismutase and U74389G on acute trimetyltin-induced cochlear dysfunction. Toxicol Appl Pharmacol 136: 236-242.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cook LL, Stine KE, Reiter LW (1984). Tin distribution in adult rat tissues after exposure to trimethyltin and triethyltin. Toxicol Appl Pharmaco 76: 344-348.[CrossRef]
  • Cossum PA, Rickert DE (1985). Metabolism of dinitrobenzenes by rat isolated hepatocytes. Drug Metab Dispos 13: 664-668.[Abstract]
  • Costa LG (1996). Biomarker research in neurotoxicology: The role of mechanistic studies to bridge the gap between the laboratory and epidemiological investigations. Environ Health Perspect 104: 55-67.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Costa LG, Manzo L. (1995). Biochemical markers of neurotoxicity: Research strategies and epidemiological applications. Toxicol Lett 77: 137-144.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Dawson R., Patterson TA, Eppler B. (1995). Endogenous excitatory amino acid release from brain slices and astrocyte cultures evoked by trimethyltin and other neurotoxic agents. Neurochem Res 20: 847-858.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Dejneka NS, Patanow CM, Polavarapu R., Toggas SM, Krady JK, Billingsley ML (1997). Localization and characterization of stannin: Relationship to cellular sensitivity to organotin compounds. Neurochem Int 31: 801-815.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Dencoff JE, Rosenberg GA, Harry GJ (1997). Trimethyltin induces gelatinase B and urokinase in rat brain. Neurosci Lett 228: 147-150.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Dey PM, Graff RD, Lagunowich LA, Reuhl KR (1994). Selective loss of the 180-kDa form of the neural cell adhesion molecule in hippocampus and cerebellum of the adult mouse following trimethyltin administration. Toxicol App Pharmacol 126: 69-74.
  • Dey PM, Polunas MA, Philbert MA, Reuhl KR (1997). Altered expression of polysialylated NCAM in mouse hippocampus following trimethyltin administration. Neurotoxicology 18: 633-643.[Web of Science][Medline] [Order article via Infotrieve]
  • Dyer RS, Walsh TJ, Wonderlan WF, Bercegay M. (1982). The trimethyltin syndrome in rats. Neurobehav Toxicol Teratol 4: 127-133.[Web of Science][Medline] [Order article via Infotrieve]
  • El-Begearmy MM, Sunde ML, Ganther HE (1977). Mutual protective effects of mercury and selenium in Japanese quail. Poul Sci 56: 313-315.[CrossRef]
  • Fan AM, Chang LW (1991). Human exposure and biological monitoring of methylmercury and selenium. In: Biological Monitoring of Exposure to Chemicals-Metals, Dillon HK, Ho MH (eds). Wiley and Sons, New York, pp 223-242.
  • Friberg L, Vostal J (eds). (1972). Mercury in the Environment. CRC Press, Cleveland, Ohio.
  • Ganey PE, Takey Y., Kaufmann FC, Thurman RJ (1990). Ethanol potentiates oxygen uptake and toxicity due to menadione bisulfite in perfused rat liver. Mol Pharmacol 38: 959-964.[Abstract]
  • Ganguly BB (1994). Bone marrow clastogenicity of trimethyltin. Mutat Res 312: 9-15.[Web of Science][Medline] [Order article via Infotrieve]
  • Ganther HE (1980). Methyl mercury toxicity and metabolism by selenium and vitamin E: Possible mechanisms. Ann NY Acad Sci 355: 212-216.[Medline] [Order article via Infotrieve]
  • Ghersi-Egea JF, Leninger-Muller B., Suleman G., Siest G., Minn A. (1994). Localization of drug-metabolizing enzyme activities to blood-brain interfaces and circumventricular organs. J Neurochem 62: 1089-1096.[Web of Science][Medline] [Order article via Infotrieve]
  • Ghersi-Egea JF, Livertoux MH (1992). Evidence for drug metabolism as a source of reactive species in the brain. EXS 62: 219-226.[Medline] [Order article via Infotrieve]
  • Ghersi-Egea JF, Livertoux MH, Minn A., Perrin R., Siest G. (1991). Enzyme mediated superoxide radical formation initiated by exogenous molecules in rat brain preparations. Toxicol Appl Pharmacol 110: 107-117.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ghersi-Egea JF, Perrin R., Leininger-Muller B., Grassiot MC, Jeandel C., Floquet J., Cuny G., Siest G., Minn A. (1993). Subcellular localization of cytochrome P450, and activities of several enzymes responsible for drug metabolism in the human brain. Biochem Pharmacol 45: 647-658.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ghosh BB, Talukder G., Sharma A. (1989). Cytotoxic effects of trimethyltin chloride on human peripheral blood lymphocytes in vitro. Hum Toxico 8: 349-353.
  • Graff RD, Falconer MM, Brown DL, Reuhl KR (1997). Altered sensitivity of posttranslationally modified microtubules to methylmercury in differentiating embryonal carcinoma-derived neurons. Toxicol Appl Pharmacol 144: 215-224.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Graff RD, Philbert MA, Lowndes HE, Reuhl KR (1993). The effect of glutathione depletion on methyl mercury-induced micro-tubule disassembly in cultured embryonal carcinoma cells. Toxicol Appl Pharmacol 120: 20-28.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Holton JL, Nolan CC, Burr SA, Ray DE, Cavanagh JB (1997). Increasing or decreasing nervous activity modulates the severity of the glio-vascular lesions of 1,3-dinitrobenzene in the rat: Effects of the tremorgenic pyrethroid, Bifenthrin, and of anaesthesia. Acta Neuropathol 93: 159-165.[CrossRef][Medline] [Order article via Infotrieve]
  • Hu HL, Bennett N., Lamb JH, Ghersi-Egea JF, Schlosshauer B., Ray DE ( 1997). Capacity of rat brain to metabolize m-dinitrobenzene: An in vitro study. Neurotoxicology 18: 363-370.[Web of Science][Medline] [Order article via Infotrieve]
  • Huang J., Philbert MA (1995). Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells. Brain Res 680: 16-22.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Huang J., Philbert MA (1996). Cellular responses of cultured cerebellar astrocytes to ethacrynic acid-induced perturbation of subcellular glutathione homeostasis. Brain Res 711: 184-192.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ikeda M., Kanai H., Akaike M., Tsutsumi S., Sadmatsu M., Masui A., Kato N. ( 1996). Nitric oxide synthase-containing neurons in the hippocampus are preserved in trimethyltin intoxication. Brain Res 712: 168-170.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Jacobs JM, Duchen LW (1980). Effects of 6-chloro-6-deoxyglucose on the nervous system of the marmoset. Neuropathol Appl Neurobiol 6: 1236-1237.
  • Jacobs JM, Ford Wcl (1981). The neurotoxicity and antifertility properties of 6-chloro-6-deoxyglucose in the mouse. Neurotoxicology 2: 405-417.[Web of Science][Medline] [Order article via Infotrieve]
  • Keller BJ, Yamanaka H., Liang DC, Kaufmann FC, Thurman RJ (1990). 02-dependent hepatotoxicity due to ethylhexanol in the perfused rat liver: Mitochondria as site of action. J Pharmacol Exp Ther 252: 1355-1360.[Abstract/Free Full Text]
  • Krady JK, Oyler GA, Balaban CD, Billingsley ML (1990). Use of avidin-biotin subtractive hybridization to characterize mRNA common to neurons destroyed by the selective neurotoxicant trimethyltin. Mol Brain Res 7: 287-297.[Medline] [Order article via Infotrieve]
  • Kuznetzov DA, Richter V. (1987). Modulation of messenger RNA metabolism in experimental methyl mercury neurotoxicity. Int J Neurosci 34: 1-17.[Web of Science][Medline] [Order article via Infotrieve]
  • Kuznetzov DA, Zavijalov NV, Govorkov AV, Ivanov-Snaryad AA (1987). Methyl mercury-induced combined inhibition of ATP regeneration and protein synthesis in reticulcyte lysate cell-free translation system. Toxicol Lett 30: 267-271.[Web of Science]
  • LeBel CP, Ali SF, McKee M., Bondy SC (1990). Organometal induced increases in oxygen radical activity: The potential of dicholorofluorescein diacetate as an index of neurotoxic damage. Toxicol Appl Pharmacol 104: 17-24.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Levesque PC, Atchison WD (1991). Disruption of brain mitochondrial calcium sequestration by methylmercury. J Pharnzacol Exp Ther 256: 236-242.
  • Levesque PC, Hare MF, Atchison WD (1992). Inhibition of mitochondrial Ca2+ release diminishes the effectiveness of methyl mercury to release acetylcholine from synaptosomes. Toxicol Appl Pharmacol 115: 11-20.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Maier WE, Brown HW, Tilson HA, Luster MI, Harry JG (1995). Trimethyltin increases interleukin (IL)-1, IL-6 and tumor necrosis factor mRNA levels in rat hippocampus. J Neuroimmunol 59: 65-75.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Maroni M., Barbieri F. (1988). Biological indicators of neurotoxicity in central and peripheral toxic neuropathies. Neurotoxicol Teratol 10: 479-484.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mason RP, Josephy PD (1985). Free radical mechanisms of nitro-reductase. In: Toxicity of Nitroaromatic Compounds, Rickert DE (ed). Hemisphere, New York, pp 121-140.
  • Mastrogiacomo F., Bergeron C., Kish SJ (1993). Brain alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease. J Neurochem 61: 2007-2014.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • McCann MJ, O'Callaghan JP, Martin PM, Bertram T., Streit WJ (1996). Differential activation of microglia and astroctyes following trimethyltin-induced neurodegeneration. Neuroscience 72: 273-281.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Monnet-Tschudi F., Zurich M., Pithon E., van Melle G., Honegger P. (1995). Microglial responsiveness as a sensitive marker for trimethyltin (TMT) neurotoxicity. Brain Res 690: 8-14.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Nieminen AL, Saylor AK, Herman B., Lemasters JJ (1994). ATP depletion rather than mitochondrial depolarization mediates hepatocyte killing after metabolic inhibition. Am J Physiol 267: C67-C74.[Web of Science][Medline] [Order article via Infotrieve]
  • Nieminen AL, Saylor AK, Tesfai SA, Herman B., Lemasters JJ (1995). Contribution of the mitochondrial permeability transition to lethal injury after exposure of hepatocytes to t-butylhydroperoxide. Biochem J 307: 99-106.[Web of Science][Medline] [Order article via Infotrieve]
  • Nolan CC, Brown AW, Cavanagh JB (1990). Regional variations in nerve cell responses to trimethyltin intoxication in Mongolian gerbils and rats; further evidence for involvement of the Golgi apparatus. Acta Neuropathol 81: 204-212.[CrossRef][Medline] [Order article via Infotrieve]
  • O'Callaghan JP (1988). Neurotypic and gliotypic proteins as biochemical markers of neurotoxicity. Neurotoxicol Teratol 10: 445-452.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • O'Connell AW, Earley B., Leonard BE (1994). The neuroprotective effect of tacarine on trimethyltin-induced memory and muscarinic receptor dysfunction in the rat. Neurochem Int 25: 555-566.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • O'Connell AW, Earley B., Leonard BE (1996). The {Phi}-ligand JO 1784 prevents trimethyltin-induced behavioral and {Phi}-receptor dysfunction in the rat. Pharmacol Toxicol 78: 296-302.[Web of Science][Medline] [Order article via Infotrieve]
  • Opacka J., Sparrow S. (1985). Nephrotic effect of trimetyltin in rats. Toxicol Lett 27: 97-102.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Pantanow CM, Day JR, Billingsley ML (1997). Alterations in hippocampal expression of SNAP-25, GAP-43, stannin and glial fibriallry acid protein following mechanical and trimethyltin-induced injury in the rat. Neuroscience 76: 187-202.[Web of Science][Medline] [Order article via Infotrieve]
  • Patel M., Ardelt BK, Yim Gkw, Isom GE ( 1990). Interaction of trimethyltin with hippocampal glutamate. Neurotoxicology 11: 601-608.[Web of Science][Medline] [Order article via Infotrieve]
  • Pavlakovic G., Kane MD, Eyer CL, Kanthasamy A., Isom GE (1995). Activation of protein kinase C by trimethyltin: Relevance to neurotoxicity. J Neurochem 65: 2338-2343.[Web of Science][Medline] [Order article via Infotrieve]
  • Philbert MA, Beiswanger CM, Waters DK, Reuhl KR, Lowndes HE (1991). Cellular and regional distribution of reduced glutathione in the nervous system of the rat: Histochemical localization by mercury orange and o-phthaldialdehyde-induced histofluorescence. Toxicol Appl Pharmacol 107: 215-227.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Philbert MA, Gray AJ, Connors TA (1987). Preliminary investigations into the involvement of the intestinal microflora in CNS toxicity induced by 1,3-dinitrobenzene in male F-344 rats. Toxicol Lett 38: 307-314.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Philbert MA, Nolan CC, Cremer JE, Tucker D., Brown AW (1987). 1,3-Dinitrobenzene-induced encephalopathy in rats. Neuropathol Appl Neurobiol 13: 371-389.[Web of Science][Medline] [Order article via Infotrieve]
  • Ray DE, Abbott NJ, Chan MW, Romero IA (1994). Increased oxidative metabolism and oxidative stress in m-dinitrobenzene neurotoxicity. Biochem Soc Trans 22: 407S.[Medline] [Order article via Infotrieve]
  • Ray DE, Brown AW, Cavanagh JB, Nolan CC, Richards HK, Wylie SP (1992). Functional/metabolic modulation of the brain stem lesions caused by 1,3-dinitrobenzene in the rat. Neurotoxicology 13: 379-388.[Web of Science][Medline] [Order article via Infotrieve]
  • Ray DE, Holton JL, Lister T., Nolan CC (1996). The glio-vascular toxicity of m-dinitrobenzene and related agents: Modulation of toxicity by neuronal activation. Arch Toxicol Suppl 18: 140-148.[Medline] [Order article via Infotrieve]
  • Reuhl KR (1991). Delayed expression of neurotoxicity: The problem of silent damage. Neurotoxicology 12: 341-346.[Web of Science][Medline] [Order article via Infotrieve]
  • Reuhl KR, Chang LW, Townsend JW (1981). Pathological effects of in utero methylmercury exposure on the cerebellum of the golden hamster. 1. Early effects upon the neonatal cerebellar cortex. Environ Res 26: 281-306.[Medline] [Order article via Infotrieve]
  • Reuhl KR, Cranmer JM (1984). Developmental neuropathology of organotin compounds. Neurotoxicology 5: 187-204.[Web of Science][Medline] [Order article via Infotrieve]
  • Romero I., Brown AW, Cavanagh JB, Nolan CC, Ray DE, Seville MP (1991). Vascular factors in the neurotoxic damage caused by 1,3-dinitrobenzene in the rat. Neuropathol Appl Neurobiol 17: 495-508.[Web of Science][Medline] [Order article via Infotrieve]
  • Romero IA, Lister T., Richards HK, Seville MP, Wylie SP, Ray DE ( 1995). Early metabolic changes during m-dinitrobenzene neurotoxicity and the possible role of oxidative stress. Free Radical Biol Med 18: 311-319.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Romero IA, Rist RJ, Chan MW, Abbott NJ (1997). Acute energy deprivation syndromes: Investigation of m-dinitrobenzene and alpha-chlorohydrin toxicity on immortalized rat brain microvessel endothelial cells. Neurotoxicology 18: 781-791.[Web of Science][Medline] [Order article via Infotrieve]
  • Ross WD, Emmett EA, Steiner J., Tureen R. (1981). Neurotoxic effects of occupational exposure to organotins. Am J Psychiatr 138: 1092-1095.[Abstract/Free Full Text]
  • Sarafian TA, Cheung MK, Verity MA (1984). In vitro methyl mercury inhibition of protein synthesis in neonatal cerebellar perikarya. Neuropathol Appl Neurobiol 10: 85-100.[Web of Science][Medline] [Order article via Infotrieve]
  • Savage MK, Reed DJ ( 1994). Oxidation of pyridine nucleotides and depletion of ATP and ADP during calcium- and inorganic phosphate-induced mitochondrial permeability transition. Biochem Biophys Res Commun 200: 1615-1620.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Schafer TJ, Atchison WD (1985). Block of 45Ca2+ uptake into synaptosomes by methylmercury: Ca2+ and Na+ dependence. J Pharmacol Exp Ther 248: 696-702.
  • Schneider H., Cervos-Navarro J. (1973). Acute gliopathy in spinal cord and brainstem induced by 6-aminonicotinamide. Acta Neuropathol 27: 11-23.
  • Slivka A., Mytilineou C., Cohen G. (1987). Histochemical evaluation of glutathione in brain. Brain Res 409: 275-284.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Slivka A., Spina MB, Cohen G. (1987). Reduced and oxidized glutathione in human and monkey brain. Neurosci Lett 74: 112-118.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Snoeij NJ, Van Iersel AAJ, Penninks AH, Seinen W. (1986). Triorganotin-induced cytotoxicity to rat thymus, bone marrow and red blood cells as determined by several in vitro assays. Toxicology 39: 71-83.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Sparber SB, O'Callaghan JP, Berra B. (1992). Ganglioside treatment partially counteracts neurotoxic effects of trimethyltin but may itself cause neurotoxicity in rats: Experimental resilts and a critical review. Neurotoxicology 13: 679-700.[Web of Science][Medline] [Order article via Infotrieve]
  • Stoewsand GS, Bache CA, Lisk DJ (1974). Dietary selenium protection of methylmercury intoxication of Japanese quail. Bull Environ Contam Toxicol 11: 152-156.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Swedish Expert Group ( 1971). Methylmercury in fish-A toxicological-epidemiological evaluation of risks. Report from an expert group. Nord Hyg Tidskrift 4(suppl): 1-8.
  • Takeuchi T. (1968). Neuropathology of Minimata disease. In: Minimata Disease, Kutsuma M (ed). Kumamoto University, Kumamoto, Japan, pp 141-228.
  • Takeuchi T. (1977). Neuropathology of Minimata disease in Kumamoto: Especially at the chronic stage. In: Neurotoxicology, Vol 1, Roizin L, Shiraki H, Grcevic N (eds). Raven Press, New York, pp 235-246.
  • Task Group on Metal Toxicity ( 1976). In: Effects and Dose-Response Relationships of Toxic Metals Norberg GF (ed). Elsevier, Amsterdam, pp 1-111.
  • Taylor TJ, Riedess F., Kocsis JJ (1973). The role of Hg2+ and methyl mercury in lipid peroxidation. Fed Proc 32: 261(A).
  • Thompson TA, Lewis JM, Dejneka NS, Severs WB, Polavarapu R., Billingsley ML (1996). Induction of apoptosis by organotin compounds in vitro: Neuronal protection with antisense oligonucleotides directed against stannin. J Pharmacol Exp Ther 276: 1201-1216.[Abstract/Free Full Text]
  • Tilson HA (1990). Neurotoxicology in the 1990s. Neurotoxicol Teratol 12: 293-300.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Toggas SM, Krady JK, Billingsley ML (1992). Molecular neurotoxicology of trimethyltin: Identification of stannin, a novel protein expressed in trimethyltin-sensitive cells. Mol Pharmacol 42: 44-56.[Abstract]
  • Tsubaki T. (1975). Studies on the Health Effects of Alkyl Mercury in Japan. Environmental Agency, Japan.
  • Vahter M., Mottet NK, Friberg L., Lind B., Shen DD, Burbacher T. (1994). Speciation of mercury in the primate blood and brain following long-term exposure to methyl mercury. Toxicol Appl Pharmacol 124: 221-229.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Verity MA (1992). Ca2+-dependent processes as mediators of neurotoxicity. In: Current Issues in Neurotoxicology, Mutti L, Costa LG, Cramner JM, Mutti A (eds). Intox Press, Little Rock, Arkansas, pp 139-147.
  • Verity MA, Serafian T. (1991). Role of oxidative injury in the pathogenesis of methyl mercury neurotoxicity. In: Advances in Mercury Toxicology, Mutti A, Manzo L, Costa LG, Cranmer JM (eds). Plenum, New York, pp 209-222.
  • Watanabe I., Iwasaki Y., Aikawa H., Satayoshi E., Davis JW (1981). Hemorrhage of thiamine-deficient encephalopathy. J Neuropathol Exp Neurol 40: 566-580.[Web of Science][Medline] [Order article via Infotrieve]
  • Welsh SO, Soares JH Jr (1972). The protective effect of vitamin E and selenium against methylmercury toxicity in the Japanese quail. Nutr Rep Int 13: 43-51.
  • Who (1976). Mercury. In: Environmental Health Criteria 1. World Health Organization, Geneva, Switzerland.
  • Xu J., Chan, MW, Ray DE ( 1997). Metabolism of m-dinitrobenzene in astrocytes and endothelial cells. Hum Exp Toxicol 16: 670.
  • Zahrebelski G., Nieminen AL, al-Ghoul K., Qian T., Herman B., Lemasters JJ (1995). Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: A laser scanning confocal microscopic study. Hepatology 21: 1361-1372.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 28, No. 1, 43-53 (2000)
DOI: 10.1177/019262330002800107
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
F. Grun, H. Watanabe, Z. Zamanian, L. Maeda, K. Arima, R. Cubacha, D. M. Gardiner, J. Kanno, T. Iguchi, and B. Blumberg
Endocrine-Disrupting Organotin Compounds Are Potent Inducers of Adipogenesis in Vertebrates
Mol. Endocrinol., September 1, 2006; 20(9): 2141 - 2155.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
F. Grun and B. Blumberg
Environmental Obesogens: Organotins and Endocrine Disruption via Nuclear Receptor Signaling
Endocrinology, June 1, 2006; 147(6): s50 - s55.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
B. E. Reese, C. Davidson, M. L. Billingsley, and J. Yun
Protein Kinase C{epsilon} Regulates Tumor Necrosis Factor-{alpha}-Induced Stannin Gene Expression
J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 61 - 69.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. E. Davidson, B. E. Reese, M. L. Billingsley, and J. K. Yun
Stannin, A Protein That Localizes to the Mitochondria and Sensitizes NIH-3T3 Cells to Trimethyltin and Dimethyltin Toxicity
Mol. Pharmacol., October 1, 2004; 66(4): 855 - 863.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
P. Gunasekar, L. Li, K. Prabhakaran, V. Eybl, J. L. Borowitz, and G. E. Isom
Mechanisms of the Apoptotic and Necrotic Actions of Trimethyltin in Cerebellar Granule Cells
Toxicol. Sci., November 1, 2001; 64(1): 83 - 89.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Philbert, M. A.
Right arrow Articles by Reuhl, K. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Philbert, M. A.
Right arrow Articles by Reuhl, K. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?