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Although there is no consensus regarding the increased activation of nicotinamide adenine dinucleotide phosphate oxidase by smoking, xanthine oxidase, an ROS-producing system, is activated by smoking

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Briefly, human in vitro systems do not reflect all aspects of cellular interaction and tissue organization, in vivo animal models do not necessarily reflect human biology in its finer details, and human clinical studies are hampered by time and cost constraints as well as accessibility to key biological samples (that are accessible in animal studies)

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