The protective effects of N-Acetl-cysteine, oxo-thiazolidine-carboxylate, acetaminophen and their combinations against sulfur mustard cytotoxicity on human skin fibroblast cell line (HF2FF).
Using human skin-fibroblast cell line HF2FF, the efficacy of some drugs was evaluated against sulfur mustard (SM) cytotoxicity. The drugs were the sulfhydryl containing molecule including N-acetylcysteine (NAC), 2-oxo-thiazolidine-4-carboxylate (OTC) and acetaminophen as glutathione (GSH) stimulator pathway.



The protective effects of NAC (0.1 mM), OTC (1.8 mM), and acetaminophen (25 mM) alone or in combination with each other were evaluated on SM (180 M)-induced cytotoxicity. NAC and OTC were applied with SM simultaneously and acetaminophen 30 min before SM exposure, incubated for 1 h and then were rinsed and incubated with fresh medium. The efficacy was evaluated by determination of cells viability, intracellular GSH level and catalase activity 1 and 24 h post SM exposure or co-treatments.



The cells viability was decreased 21.8% and 55.2%, respectively for 1 and 24 h post SM (1 h exposure) incubation. So, the 1-h SM exposure and 24-h treatment incubation were selected for evaluation. While, NAC alone treatment increased the cells viability (25%), GSH level (320%) and catalase activity (18%), the most effective combination was NAC plus OTC and acetaminophen which increased more significantly the cells viability (about 40%), GSH level (470%) and catalase activity (100%).



The most effective combination was NAC (0.1 mM) plus OTC (1.8 mM) and acetaminophen (25 mM) which should be used before or concomitant with SM exposure. These drugs may reduce SM toxicity possibly by increment of GSH level and catalase activity. This efficacy needs to be confirmed by in vivo study.
Saberi
Mehdi
M
Dept. of Pharmacology and Toxicology, Chemical Injury Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Zaree Mahmodabady
Ali
A
Dept. of Biochemistry, Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
D000082:Acetaminophen / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity; D019610:Cytoprotection; D004347:Drug Interactions; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009151:Mustard Gas / Q000633:toxicity*; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology*; D012867:Skin / Q000166:cytology; D053778:Thiazolidines / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D002619:Chemical Warfare Agents; D016166:Free Radical Scavengers; D053778:Thiazolidines; D000082:Acetaminophen; D002374:Catalase; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; D009151:Mustard Gas; D000111:Acetylcysteine; C029536:2-oxothiazolidine-4-carboxylic acid