N-Acetylcysteine as a treatment for sulphur mustard poisoning

Abstract

In the long and intensive search for effective treatments to counteract the toxicity of the chemical warfare (CW) agent sulphur mustard (H; bis(2-chloroethyl) sulphide), the most auspicious and consistent results have been obtained with the drug N-acetylcysteine (NAC), particularly with respect to its therapeutic use against the effects of inhaled H. It is a synthetic cysteine derivative that has been used in a wide variety of clinical applications for decades and a wealth of information exists on its safety and protective properties against a broad range of toxicants and disease states. Its primary mechanism of action is as a pro-drug for the synthesis of the antioxidant glutathione (GSH), particularly in those circumstances where oxidative stress has exhausted intracellular GSH stores. It impacts a number of pathways either directly or through its GSH-related antioxidant and anti-inflammatory properties, which make it a prime candidate as a potential treatment for the wide range of deleterious cellular effects that H is acknowledged to cause in exposed individuals. This report reviews the available literature on the protection afforded by NAC against the toxicity of H in a variety of model systems, including its efficacy in treating the long-term chronic lung effects of H that have been demonstrated in Iranian veterans exposed during the Iran-Iraq War (1980-1988). Although there is overwhelming evidence supporting this drug as a potential medical countermeasure against this CW agent, there is a requirement for carefully controlled clinical trials to determine the safety, efficacy and optimal NAC dosage regimens for the treatment of inhaled H.

HMSCs exosome‐derived miR‐199a‐5p attenuates sulfur mustard‐associated oxidative stress via the CAV1/NRF2 signalling pathway

“…NAC has a strong direct antioxidant activity and maintains the intracellular GSH level. Thus, it is recognized as the primary medicine candidate for treating pulmonary toxicity caused by SM 34 . The injury caused by oxidative stress is the key link of acute and chronic SM damage 20 .…”

The effect of different drugs on hard metal lung disease in a rat model

“…It acts extracellularly to reduce cystine to cysteine, allowing faster transportation into the cell for use in the biosynthesis of GSH, improving the cellular redox state. By facilitating GSH biosynthesis, NAC serves an indirect anti-oxidant role while also having a direct anti-oxidant action, acting as a powerful scavenger of hard metal (Sawyer, 2020; Kiss et al, 2021). It is unclear, therefore, why NAC, with known anti-oxidant activity, was ineffective against hard metal disease in this model.…”

HMSCs exosome-derived miR-199a-5p attenuates sulfur mustard-associated oxidative stress via the CAV1/NRF2 signaling pathway

“…NAC has a strong direct antioxidant activity and maintains the intracellular GSH level. Thus, it is recognized as the primary medicine candidate for treating pulmonary toxicity caused by SM [35]. The injury caused by oxidative stress is the key link of acute and chronic SM damage [36].…”