N-Acetyl cysteine abrogates silver-induced reactive oxygen species in human cells without altering silver-based

Kush N Shah1, Parth N Shah1, Andrew R Mullen2

  • 1Department of Microbial Pathogenesis & Immunology, Texas A&M University Health Science Center, College Station, TX, USA.

Toxicology Letters
|July 14, 2020
PubMed

Insights

N-acetyl cysteine (NAC) prevents silver toxicity in lung cells by reducing reactive oxygen species (ROS) and preserving metabolic function. NAC also binds silver without affecting its antimicrobial properties, offering a potential protective agent for aerosolized silver treatments.

Area of Science:

  • Biomedical research
  • Antimicrobial agents
  • Toxicology

Background:

  • Silver-based antimicrobials are effective against multi-drug resistant (MDR) pathogens.
  • Topical silver use is expanding to aerosolized treatments for lung infections.
  • Silver-induced respiratory toxicity is a concern, primarily mediated by reactive oxygen species (ROS).

Purpose of the Study:

  • To investigate the protective effects of antioxidants against silver toxicity in bronchial epithelial cells.
  • To identify potential prophylactic agents to mitigate silver-induced lung toxicity.
  • To understand the mechanisms underlying NAC's protective action.

Main Methods:

  • Exposure of bronchial epithelial cells to silver acetate.
  • Evaluation of ROS generation and cellular metabolic activity.
  • Assessment of antioxidant candidates: N-acetyl cysteine (NAC), ascorbic acid, and melatonin.
  • Measurement of citric acid cycle metabolites and adenosine triphosphate (ATP) levels.
  • Analysis of NAC's direct binding to silver and its effect on antimicrobial activity.

Main Results:

  • Silver acetate exposure induced ROS generation and toxicity in bronchial epithelial cells.
  • NAC was the only antioxidant that effectively abrogated ROS production and rescued cells from toxicity.
  • NAC pretreatment preserved metabolic activity, maintaining normal citric acid cycle function and elevated ATP levels.
  • NAC demonstrated a dual protective mechanism: antioxidant activity and direct silver binding.
  • NAC binding to silver did not compromise the antimicrobial efficacy of silver acetate.

Conclusions:

  • N-acetyl cysteine (NAC) shows significant promise as a prophylactic agent against silver-induced respiratory toxicity.
  • NAC's protective effects stem from its antioxidant properties and direct silver-binding capacity.
  • NAC can be a valuable adjunct for aerosolized silver antimicrobial therapies, ensuring safety without sacrificing efficacy.

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