Efficient protection of human bronchial epithelial cells against sulfur and nitrogen mustard cytotoxicity using drug

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Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices
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Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices

Published on: May 9, 2018

S Rappeneau1, A Baeza-Squiban, F Marano

  • 1Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Université Paris VII Denis-Diderot, Tour 53-54, E3 case 7073, 2 place Jussieu, 75251 Paris cedex 05, France. rappeneau@paris7.jussieu.fr

Toxicological Sciences : an Official Journal of the Society of Toxicology
|October 29, 2000
PubMed

Insights

Researchers tested molecules to protect against sulfur mustard (SM) and nitrogen mustard (HN2) using lung cells. Combinations like N-acetyl-cysteine (NAC) and doxycycline (DOX) showed promise, especially for delayed protection against SM.

Area of Science:

  • Chemical warfare agent countermeasures
  • Cellular toxicology and protection mechanisms

Background:

  • Sulfur mustard (SM) and nitrogen mustard (HN2) are cytotoxic chemical warfare agents.
  • Understanding mustard cytotoxicity mechanisms is crucial for developing effective antidotes.
  • Previous studies explored various molecules for mustard decontamination and protection.

Purpose of the Study:

  • To evaluate the efficacy of candidate molecules in protecting human bronchial epithelial cells (16HBE14o-) against SM and HN2.
  • To identify effective single agents and combinations for immediate and delayed post-exposure treatment.
  • To find promising therapeutic strategies, particularly those using agents with existing human therapy applications.

Main Methods:

  • Human bronchial epithelial cells (16HBE14o-) were exposed to 100 microM HN2 or SM.
  • Candidate molecules including N-acetyl-cysteine (NAC), WR-1065, hexamethylenetetramine (HMT), niacinamide (NC), dimethylthiourea (DMTU), L-thiocitrulline (L-TC), L-nitroarginine methyl ester (L-NAME), and doxycycline (DOX) were tested.
  • Cell viability was assessed 24 hours post-exposure using the WST-1 assay; combination therapies and delayed treatments were also investigated.

Main Results:

  • Individual agents showed selective efficacy: DMTU and WR-1065 protected against HN2, DOX against SM, while NAC and L-TC were effective against both.
  • Combinations were necessary to improve protection against SM, with (L-TC + DOX), (NAC + DOX), (NAC + DMTU), (NAC + HMT), and (NC + DOX) showing effectiveness.
  • The combination of NAC + DOX demonstrated significant efficacy in delayed cotreatment (up to 90 minutes) against SM.

Conclusions:

  • N-acetyl-cysteine (NAC) and doxycycline (DOX) combination therapy shows significant potential for treating sulfur mustard exposure, even with delayed administration.
  • This NAC + DOX combination is particularly promising due to the established use of these agents in human medicine.
  • Further research into combined therapeutic strategies is warranted for effective countermeasures against mustard agents.

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