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A series of studies have shown association linking cigarette smoking and nicotine toxicity to glutathione depletion within periodontal tissues.[4] Studies of betel nut chewing, and periodontitis have shown that arcea nut alkaloid, arecoline-induced thiol depletion in periodontal ligament fibroblasts may render them more susceptible to the effects of nicotine;[57,58] glutathione protection negated nicotine toxicity;[41] and that cigarette smoke decreased periodontal ligament fibroblast glutathione levels in a dose-dependent manner and stimulated stress-specific genes.[44] As already discussed, GST is xenobiotic metabolizing enzyme required for the detoxification reactions and utilizes free glutathione