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Mode of Cell Death in Mouse Brain Following Early Exposure to Low-Dose Trichloroethane: Apoptosis or Necrosis
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Volume 3, 2015
Issue 6 (December)
Pages: 232-240   |   Vol. 3, No. 6, December 2015   |   Follow on         
Paper in PDF Downloads: 38   Since Oct. 24, 2015 Views: 1241   Since Oct. 24, 2015
Mohamed A. Al-Griw, Division of Developmental Biology, Zoology Department, Faculty of Science, University of Tripoli, Tripoli, Libya.
Abdul Hakim Elnfati, Division of Developmental Biology, Zoology Department, Faculty of Science, University of Tripoli, Tripoli, Libya.
Naser M. Salama, Division of Developmental Biology, Zoology Department, Faculty of Science, University of Tripoli, Tripoli, Libya.
Massaud S. Maamar, Division of Developmental Biology, Zoology Department, Faculty of Science, University of Tripoli, Tripoli, Libya.
Soad A. Treesh, Department of Histology and Medical Genetics, Faculty of Medicine, University of Tripoli, Tripoli, Libya.
Taher Shaibi, Division of Ecological Sciences, Zoology Department, Faculty of Science, University of Tripoli, Tripoli, Libya; National Centre for Disease Control, Ministry of Health, Tripoli, Libya.
The goal of this study was to investigate, in-vivo, the predominant mechanism of cell death, apoptosis versus necrosis, in the mature mouse brain exposed early to a ubiquitous environmental toxicant trichloroethane (TCE). A subset of male albino mice was injected intraperitoneally twice weekly for three weeks with TCE (100 and 400µg/kg). All animals were followed up for signs of toxicity and mortality. Changes in neural tissues were histpathologically evaluated. Biomarkers of brain cell number were also studied. The results showed that TCE insult triggered significant alterations in the microstructure of the brain tissues compared to controls. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates that cell apoptosis with necrosis was evident in the TCE-treated groups. The percent of necrosis was quantified as 20.09 ± 2.57% at 100µg/kg TCE, 30.57 ± 5.18% at 400µg/kg TCE, and 12.67 ± 1.25% in controls. However, the percent of apoptosis was quantified as 29.18 ± 1.51% at 100µg/kg TCE, 20.14 ± 2.12% at 400µg/kg TCE, and 8 ± 1.25% in controls. There was also a significant reduction in the brain DNA content in the TCE-treated groups. Agarose gel electrophoresis is also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation. These results correlated with neurobehavioral impairment. These findings indicate that TCE induces degeneration and apoptotic cell death in mouse brain, suggesting a crucial role played by apoptosis in TCE neurotoxicity.
Trichloroethane, Neurotoxicity, Neurobehavior Abnormalities, Apoptosis, DNA Fragmentation, Mouse
Sadowski, R. N., Wise, L.M., Park, P.Y., Schantz, S.L., Jurask, J.M. (2014) Early Exposure to Bisphenol A alters Neuron and Glia Number in the Rat Prefrontal Cortex of Adult Males, but not Females, Neuroscience 279, 122-131.
House, R. A., Liss, G.M., Wills, M.C., Holness, D.L. (1996) Paresthesias and sensory neuropathy due to 1,1,1-trichloroethane, Journal occupational environmental Medicine 38, 123-124.
Snyder, R., Andrews, L.S. (1996) Toxic effects of solvents and vapors. In: Klaassen, CD; ed. Casarett and Doull’s Toxicology: The Basis Science of Poisons, 5th ed. New York: McGraw-Hill.
York, R. G., Sowry, B.M., Hastings, L., Manson, J.M. (1982) Evaluation of teratogenicity and neurotoxicity with maternal inhalation exposure to methyl chloroform, Journal of Toxicol. environ. Health 9, 251-266.
Maurissen, J. P., Shankar, M.R., Zielke, G.J. (1994) Lack of developmental cognitive and other neurobehavioral effects following maternal exposure to 1,1,1-trichloroethane in rats, Toxicologist 14, 163.
Botancourt, A. M., Mobley, J. A., Russo, J., and Lamartiniere, C. A. (2010) Proteomic analysis in mammary glands of rat offspring exposed in utero to bisphenol A, Journal of Proteomics 73, 1241-1253.
Wang, G., Wang, J., Ma, H., Ansari, G. A. S., and Khan, M. F. (2013) N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress, Toxicology and Applied Pharmacology 273, 189-195.
Warren, D. A., Reigle, T. G., Muralidhara, S., and Dallas, C. (1998) Schedule-controlled operant behavior of rats during 1,1,1-trichloroethane inhalation: relationship to blood and brain solvent concentrations, Neurotoxicol Teratology 20, 143-153.
ATSDR. Toxicological Profile for 1,1,1-trichloroethane (update). U.S. Department of Health and Human Services, Public Health Service. August 1995.
Mackay, C. J., Campbell, L., Samuel, A. M., Alderman, K. J., Idzikowski, C., Wilson, H. K., and Gompertz, D. (1987) Behavioral changes during exposure to 1,1,1-trichloroethane: Time-course and relationship to blood solvent levels, American Journal Ind. Medicine 11, 223-239.
Mackay, C. J., Campbell, L., Samuel, A.M. (1987) Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels, American Journal Ind Medicine 11, 223–239.
Orrenius, S., Nicotera, P., and Zhivotovsky, B. (2010) Cell Death Mechanisms and Their Implications in Toxicology, Toxicological Sciences 119, 3-19.
Li, Z., Jo, J., Jia, J. M., Lo, S. C., Whitcomb, D. J., Jiao, S., Cho, K., and Sheng, M. (2010) Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization, Cell 141, 859-871.
Healy, E., Dempsey, M., Lally, C., Ryan, M.P. (1998) Apoptosis and necrosis: mechanisms of cell death induced by cyclosporine A in a renal proximal tubular cell line, Kidney Int. 54, 1955-1966.
Vanden Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H, Vandenabeele, P. (2014) Regulated necrosis: the expanding network of non-apoptotic cell death pathways, Nat Rev Mol Cell Biology 15, 135-147.
Rhodes, M. C., Seidler, F. J., Qiao, D., Tate, C. A., Cousins, M. M., and Slotkin, T. A. (2004) Does pharmacotherapy for preterm labor sensitize the developing brain to environmental neurotoxicants? Cellular and synaptic effects of sequential exposure to terbutaline and chlorpyrifos in neonatal rats, Toxicology and Applied Pharmacology 195, 203-217.
Winick, M., and Noble, A. (1965) Quantitative changes in DNA, RNA and protein during prenatal and postnatal growth in the rat, Dev. Biology 12, 451-466.
Qiao, D., Seidler, F. J., Padilla, S., and Slotkin, T. A. (2002) Developmental neurotoxicity of chlorpyrifos: what is the vulnerable period? Environ, Health Perspect. 110, 1097-1103.
Qiao, D., Seidler, F. J., Tate, C. A., Cousins, M. M., and Slotkin, T. A. (2003) Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood, Environ. Health Perspect 111, 536- 544.
Kjellstrom, T., and Nordberg, G. F. (1978) A kinetic model of cadmium metabolism in the human being, Environmental Research 16, 248-269.
Al-Griw, M. A., Salama, N. M., Treesh, S. A., Algadi, L. N., and Elnfati, A. H. (2015) Cell Death in Mouse Brain following Early Exposure to Trichloroethane (TCE), International Journal of Advanced Research 3, 1424-1430.
Melani, A., Pantoni, L., and Bordoni, F. (2003) The selective A2A receptor antagonist SCH 58261 reduces striatal transmitter outflow, turning behavior and ischemic brain damage induced by permanent focal ischemia in the rat, Brain Research 959, 243-250.
Wang, W., Hafner, K. S., and Flaws, J. A. (2014) In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse, Toxicology and Applied Pharmacology 276, 157-164.
Garcia, J. H., Wagner, S., Liu, K. F., and Hu, X. J. (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation, Stroke 26, 627-634.
Peinado, M., Quesada, A., Pedrosa, J., MartenZ, M. Esteban, F.J., Moral, M.L., Peinado, J.M. (1997) Light Microscopic Quantification of Morphological Changes During Aging in Neurons and Glia of the Rat Parietal Cortex, The Anatomical Record 247, 420-425.
Koss, W. A., Sadowski, R.N., Sherrill, L.K., Gulley, J.M., Juraska, J.M. (2012) Effects of ethanol during adolescence on the number of neurons and glia in the medial prefrontal cortex and basolateral amygdala of adult male and female rats, Brain Research 1466, 24-32.
Kwon, B. K., Liu, J., Messerer, C., Kobayashi, N. R., McGraw, J., Oschipok, L., and Tetzlaff, W. (2002) Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury, PNAS 99, 3246–3251.
Gujral, J. S., Knight, T. R., Farhood, A., Bajt, M. L., and Jaeschke, H. (2002) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis?, Toxicological Sciences 67, 322-328.
Murata, K., Inoue, O., Akutsu, M. (2010) Neuromotor effects of short-term and long-term exposures to trichloroethylene in workers, Am J Ind Med 53, 915-921.
Kulig, B. M. (1987) The effects of chronic trichloroethylene exposure on neurobehavioral functioning in the rat, Neurotoxicol Teratology 9, 171-178.
Lane, R. W., Riddle, B.L.; Borzelleca, J.F. (1982) Effects of 1,2-dichloroethane and 1,1,1-trichloroethane in drinking water on reproduction and development in mice. , Toxicol Appl Pharmacology 63, 409–421.
Nilsson, K. B. (1987) Effects of 1,1,1-trichloroethane on synaptosomal calcium accumulation in mouse brain, Pharmacol Toxicology 61, 215–219.
Kumar, P., Prasad, A.K., Mani, U. (2001) Trichloroethylene induced testicular toxicity in rats exposed by inhalation, Hum Exp Toxicology 20, 585-589.
Wyllie, A. (1981) Cell death: A new classification separating apoptosis from necrosis. In: Bowen ID LR, ed. Cell death in biology and pathology, Chapman and Hall: London, England, 9-34.
Raff, M. C., Barres, B.A., Burne, J.F., Coles, H.S., Ishizaki, Y. and Jacobson, M.D. (1993) Programmed cell death and the control of cell survival: lessons from the nervous system, Science 262 695-700.
Kerr, J. F., Wyllie, A. H., and Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics, Br J Cancer 26, 239-257.
Wu, A., and Liu, Y. (2000) Apoptotic cell death in rat brain following deltamethrin treatment, Neuroscience Letters 279, 85-88.
Thompson, C. B. (1995) Apoptosis in the pathogenesis and treatment of disease, Science 267 1456-1462.
Rosengren, L. E., Aurell, A., Kjellstrand, P. (1985) Astrogliosis in the cerebral cortex of gerbils after long-term exposure to 1,1,1-trichloroethane, Scand J Work Environ Health 11, 447–456.
Karlsson, J. E., Rosengren, L.E., Kjellstrand, P. (1987) Effects of low-dose inhalation of three chlorinated aliphatic organic solvents on deoxyribonucleic acid in gerbil brain. Scand J Work Environ Health, 13, 453–458.
Haglid, K. G., Rosengren, L.E., Karlsson, J.E. E. (1990) ffects of low-dose inhalation of three chlorinated aliphatic organic solvents on deoxyribonucleic acid in gerbil brain. Reply to comments, Scand J Work Environ Health 16, 145-146.
Conti, A. C., Raghupathi, R., Trojanowski, J.Q. and McIntosh, T.K. (1998) Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period, Journal of Neuroscience 18, 5663-5672.
Collins, R. J., Harmon, B.V., Gobe, G.C. and Kerr, J.F. (1992) Internucleosomal DNA cleavage should not be the sole criterion for identifying apoptosis, Int. J. Radiat. Biology 61, 451-453.
Levin, E. D., Addy, N., Baruah, A., Elias, A., Christopher, N.C., Seidler, F.J., Slotkin, T.A. (2002) Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations., Neurotoxicol Teratology 24, 733-741.
Roy, T. S., Seidler, F.J., Slotkin, T.A. (2002) Prenatal nicotine exposure evokes alterations of cell structure in hippocampus and somatosensory cortex, Journal of Pharmacol. Exp. Ther. 300, 124-133.
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