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Testicular germ-cell apoptosis in stressed rats following combined exposure to pyridostigmine bromide, N,N-diethyl m-toluamide (DEET), and permethrin.

Publication ,  Journal Article
Abou-Donia, MB; Suliman, HB; Khan, WA; Abdel-Rahman, AA
Published in: J Toxicol Environ Health A
January 10, 2003

This study reports and characterizes the testicular apoptosis following daily exposure of male Sprague-Dawley rats to subchronic combined doses of pyridostigmine bromide (PB, 1.3 mg/kg/d in water, oral), a drug used for treatment of myasthenia gravis and prophylactic treatment against nerve agents during the Persian Gulf War; the insect repellent N,N-diethyl m-toluamide (DEET, 40 mg/kg/d in ethanol, dermal); and the insecticide permethrin (0.13 mg/kg in ethanol, dermal), with and without stress for 28 d. Combined exposure to these chemicals was implicated in the development of illnesses including genitourinary disorders among many veterans of the Persian Gulf War. Previous studies from this laboratory have shown that exposure to combination of these chemicals produced greater toxicity compared to single components. Exposure to stress alone did not cause any significant histopathological alterations in the testes. Administration of combination of these chemicals induced apoptosis in rat testicular germ cells, Sertoli cells, and Leydig cells, as well as in the endothelial lining of the blood vessels. Testicular damage was significantly augmented when the animals were further exposed to a combination of chemicals and stress. Histopathological examination of testicular tissue sections showed that apoptosis was confined to the basal germ cells and spermatocytes, indicating suppression of spermatogenesis. Increased apoptosis of testicular cells coincided, in timing and localization, with increased expression of the apoptosis-promoting proteins Bax and p53. Furthermore, significant increase of 3-nitrotyrosine immunostaining in the testis revealed oxidative and/or nitrosation induction of cell death. In conclusion, combined exposure to real-life doses of test compounds caused germ-cell apoptosis that was significantly enhanced by stress.

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Published In

J Toxicol Environ Health A

DOI

ISSN

1528-7394

Publication Date

January 10, 2003

Volume

66

Issue

1

Start / End Page

57 / 73

Location

England

Related Subject Headings

  • Toxicology
  • Testis
  • Stress, Physiological
  • Rats, Sprague-Dawley
  • Rats
  • Pyridostigmine Bromide
  • Pyrethrins
  • Male
  • Insecticides
  • Insect Repellents
 

Citation

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ICMJE
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Abou-Donia, M. B., Suliman, H. B., Khan, W. A., & Abdel-Rahman, A. A. (2003). Testicular germ-cell apoptosis in stressed rats following combined exposure to pyridostigmine bromide, N,N-diethyl m-toluamide (DEET), and permethrin. J Toxicol Environ Health A, 66(1), 57–73. https://doi.org/10.1080/15287390306463
Abou-Donia, Mohamed B., Hagir B. Suliman, Wasiuddin A. Khan, and Ali A. Abdel-Rahman. “Testicular germ-cell apoptosis in stressed rats following combined exposure to pyridostigmine bromide, N,N-diethyl m-toluamide (DEET), and permethrin.J Toxicol Environ Health A 66, no. 1 (January 10, 2003): 57–73. https://doi.org/10.1080/15287390306463.
Abou-Donia MB, Suliman HB, Khan WA, Abdel-Rahman AA. Testicular germ-cell apoptosis in stressed rats following combined exposure to pyridostigmine bromide, N,N-diethyl m-toluamide (DEET), and permethrin. J Toxicol Environ Health A. 2003 Jan 10;66(1):57–73.
Abou-Donia, Mohamed B., et al. “Testicular germ-cell apoptosis in stressed rats following combined exposure to pyridostigmine bromide, N,N-diethyl m-toluamide (DEET), and permethrin.J Toxicol Environ Health A, vol. 66, no. 1, Jan. 2003, pp. 57–73. Pubmed, doi:10.1080/15287390306463.
Abou-Donia MB, Suliman HB, Khan WA, Abdel-Rahman AA. Testicular germ-cell apoptosis in stressed rats following combined exposure to pyridostigmine bromide, N,N-diethyl m-toluamide (DEET), and permethrin. J Toxicol Environ Health A. 2003 Jan 10;66(1):57–73.
Journal cover image

Published In

J Toxicol Environ Health A

DOI

ISSN

1528-7394

Publication Date

January 10, 2003

Volume

66

Issue

1

Start / End Page

57 / 73

Location

England

Related Subject Headings

  • Toxicology
  • Testis
  • Stress, Physiological
  • Rats, Sprague-Dawley
  • Rats
  • Pyridostigmine Bromide
  • Pyrethrins
  • Male
  • Insecticides
  • Insect Repellents