Mohamed Bahie Abou-Donia

Mohamed Bahie Abou-Donia

Professor of Pharmacology and Cancer Biology

External Address: 
308 Research Drive, Room C173, Durham, NC 27710
Internal Office Address: 
Duke Box 3813, Durham, NC 27710
Phone: 
919.684.2221

Overview

The overall research program in this laboratory is directed toward understanding the basic mechanisms by which chemicals adversely affect the nervous system. This should lead to a better assessment of acute and chronic neurotoxicities and the development of drugs to prevent or treat them. We are primarily concerned with neurotoxicants that produce Wallerian-type degeneration of the axon and myelin of the central and peripheral nervous systems. These chemicals include antiesterase organophosphorus compounds, aliphatic hydrocarbons, acrylamide, and carbon disulfide. These studies are being carried out in vivo and in vitro using cell culture systems, i.e., primary cultures of bovine adrenomedullary chromaffin cells and the rat pheochromocytoma PC 12 cells.

The role of kinase-dependent phosphorylation of cytoskeletal proteins in the pathogenesis of these neurotoxicants is being studied. The involvement of calcium-Calmodulin kinase II in the mechanism of organophosphorus compound-induced delayed neurotoxicity is under investigation. We are studying the multiple mechanisms responsible for the accumulation of neurofilaments above nodes of Ranvier in the distal axon, a pathognomonic feature of aliphatic hexacarbon- and acrylamide-induced neurotoxicities, i.e., inhibition of a kinase inhibition of a protease, or crosslinking of neurofilaments.

We are also examining the role of pharmacokinetics and metabolism of neurotoxicants in age-sensitivity and species selectivity that are characteristic of these neuropathies. The metabolic activation and inactivation of neurotoxic chemicals by specific cytochrome P-450 isozymes are being investigated.

An interesting characteristic of neurotoxic chemicals that induce Wallerian-type degeneration of the nervous system is the ability to cause male reproductive toxicity. Recently, we have confirmed this phenomenon with organophosphorus compounds and characterized the male reproductive toxicity of tri-o-cresyl phosphate.

Recently, we have been investigating the mechanisms that may be involved in the Persian Gulf War Veterans' illnesses. We are studying the hypothesis that this condition is related to the acute cholinergic and delayed neurotoxicity resulting from coexposure to multiple chemicals including organophosphorus esters and prophylactic treatments with various drugs. Our previous studies have demonstrated that combined exposure to large doses of chemicals produced greater toxicity than that produced by single components. In March of this year, we were awarded a grant from the Department of Defense to expand our previous findings to include doses low enought to be representative of human exposure levels. We are investigating the long term effects of sub-clinical exposure to the nerve agent, saran, along and in combination with the prophylactic drug, pyridostigmine burmide and the insect repellant DEET as well as the insecticide permethrin in the presence or absence of stress. Neurologic defects are being evaluated by clinical condition, neurobehavior, integrity of teh blood brain barrier, and electrophysiological changes. We also plan to study the effect of these treatments on the level of actylcholinestisase as well as the cholinergic expression.

Education & Training

  • Ph.D., University of California at Berkeley 1967

Selected Grants

The Use of B-Cell Depletion Therapy (BCDT) in Gulf War Illness: A Phase I/II Study awarded by Nova Southeastern University (Principal Investigator). 2018 to 2020

Novel auto antibody serum and cerebrospinal fluid Biomarkers in veterans with Gulf War Illness awarded by Department of Defense (Principal Investigator). 2015 to 2020

Developmental neurotoxicity in Offspring Following Combined Maternal Exposure to Nocotine and Chlorpyrifo awarded by Environmental Protection Agency (Principal Investigator). 2001 to 2005

Biomonitoring Of Pesticide Contamination awarded by National Science Foundation (Principal Investigator). 1998 to 2001

Mechanisms of Occupational Neuropathies awarded by National Institutes of Health (Principal Investigator). 1996 to 2000

Animal Models Of Organophosphate Toxcicity awarded by Environmental Protection Agency (Principal Investigator). 1997 to 1998

Animal Models Of Organophosphate Toxicity awarded by Environmental Protection Agency (Principal Investigator). 1995 to 1998

Pages

Abou-Donia, M. B. Mammalian Toxicology. 2015, pp. 1–679. Scopus, doi:10.1002/9781118683484. Full Text

Abou-Donia, M. B. “Neurotoxicity.” Mammalian Toxicology, 2015, pp. 395–423. Scopus, doi:10.1002/9781118683484.ch18. Full Text

Abou-Donia, M. B., and M. Salama. “Food Additives.” Mammalian Toxicology, 2015, pp. 269–87. Scopus, doi:10.1002/9781118683484.ch13. Full Text

El-Masry, E. M., and M. B. Abou-Donia. “Naturally Occurring Toxins.” Mammalian Toxicology, 2015, pp. 605–40. Scopus, doi:10.1002/9781118683484.ch27. Full Text

Abou-Donia, M. B. “Metabolic Biotransformation of Xenobiotics.” Mammalian Toxicology, 2015, pp. 101–29. Scopus, doi:10.1002/9781118683484.ch6. Full Text

Abou-Donia, M. B. “Pesticides.” Mammalian Toxicology, 2015, pp. 131–70. Scopus, doi:10.1002/9781118683484.ch7. Full Text

Abou-Donia, M. B. “General Principles.” Mammalian Toxicology, 2015, pp. 1–14. Scopus, doi:10.1002/9781118683484.ch1. Full Text

Abou-Donia, M. B. “Toxicology in the 21st Century.” Mammalian Toxicology, 2015, pp. 641–50. Scopus, doi:10.1002/9781118683484.ch28. Full Text

Abou-Donia, M. B. “Gases.” Mammalian Toxicology, 2015, pp. 219–32. Scopus, doi:10.1002/9781118683484.ch10. Full Text

Abou-Donia, M. B. “Drugs of Abuse.” Mammalian Toxicology, 2015, pp. 579–603. Scopus, doi:10.1002/9781118683484.ch26. Full Text

Abou-Donia, M. B., et al. “Metabolism and toxicokinetics of xenobiotics.” Handbook of Toxicology, Second Edition, 2001, pp. 761–825.

Abou-Donia, Mohamed B., et al. “De novo Blood Biomarkers in Autism: Autoantibodies against Neuronal and Glial Proteins..” Behav Sci (Basel), vol. 9, no. 5, Apr. 2019. Pubmed, doi:10.3390/bs9050047. Full Text

Ratner, Marcia H., et al. “Amyotrophic lateral sclerosis-A case report and mechanistic review of the association with toluene and other volatile organic compounds..” Am J Ind Med, vol. 61, no. 3, Mar. 2018, pp. 251–60. Pubmed, doi:10.1002/ajim.22791. Full Text

El Rahman, Heba Allah Abd, et al. “A Panel of Autoantibodies Against Neural Proteins as Peripheral Biomarker for Pesticide-Induced Neurotoxicity..” Neurotox Res, vol. 33, no. 2, Feb. 2018, pp. 316–36. Pubmed, doi:10.1007/s12640-017-9793-y. Full Text

Abou-Donia, Mohamed Bahie, et al. “Neural autoantibodies in patients with neurological symptoms and histories of chemical/mold exposures..” Toxicol Ind Health, vol. 34, no. 1, Jan. 2018, pp. 44–53. Pubmed, doi:10.1177/0748233717733852. Full Text

Salama, Mohamed, et al. “Tubulin and Tau: Possible targets for diagnosis of Parkinson's and Alzheimer's diseases..” Plos One, vol. 13, no. 5, 2018. Pubmed, doi:10.1371/journal.pone.0196436. Full Text

Abou-Donia, Mohamed B., et al. “Screening for novel central nervous system biomarkers in veterans with Gulf War Illness..” Neurotoxicol Teratol, vol. 61, May 2017, pp. 36–46. Pubmed, doi:10.1016/j.ntt.2017.03.002. Full Text

Abou-Donia, Mohamed B., et al. “Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review..” Crit Rev Toxicol, vol. 46, no. 10, Nov. 2016, pp. 845–75. Pubmed, doi:10.1080/10408444.2016.1220916. Full Text

Abou-Donia, M. B., et al. “Propetamphos enhances chlorpyrifos-induced organophosphate-induced delayed neurotoxicity (OPIDN) in Hens: a role for plasma butyrylcholinesterase.” Toxicological and Environmental Chemistry, vol. 98, no. 8, Sept. 2016, pp. 924–41. Scopus, doi:10.1080/02772248.2016.1140384. Full Text

Abou-Donia, M. B., et al. “Autoantibodies against cytoskeletal neuronal proteins in sera of arsenic-exposed subjects correlate with neurological symptoms.” Toxicological and Environmental Chemistry, vol. 95, no. 5, May 2013, pp. 823–36. Scopus, doi:10.1080/02772248.2013.796787. Full Text

Abou-Donia, Mohamed B., et al. “Autoantibodies to nervous system-specific proteins are elevated in sera of flight crew members: biomarkers for nervous system injury..” J Toxicol Environ Health A, vol. 76, no. 6, 2013, pp. 363–80. Pubmed, doi:10.1080/15287394.2013.765369. Full Text

Pages

Brahmajothi, Mulugu V., and Mohamed B. Abou-donia. “P164 Repetitive in-vitro exposure to DFP affects MHC class I and class II antigen expression.” Human Immunology, vol. 79, Elsevier BV, 2018, pp. 187–187. Crossref, doi:10.1016/j.humimm.2018.07.221. Full Text

Abou-Donia, M. B., et al. “Developmental effects of maternal exposure to nicotine and chlorpyrifos, alone and in combination in rats..” Toxicological Sciences, vol. 72, OXFORD UNIV PRESS, 2003, pp. 127–127.

Abdel-Rahman, A. A., et al. “Sub-acute sarin exposure leads to neuropathological and neurochemical changes in the rat brain: Dose-response relationships..” Toxicological Sciences, vol. 72, OXFORD UNIV PRESS, 2003, pp. 74–74.

Abou-Donia, M. B., et al. “Acute exposure to sarin increases blood brain barrier permeability AND induces neuropathological changes in the rat brain: Dose response relationship.” Neurotoxicology, vol. 24, no. 2, ELSEVIER SCIENCE BV, 2003, pp. 299–300.