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This creates a well-documented vicious cycle: stress increases histamine release, histamine amplifies nervous system reactivity (histamine H3 receptors modulate neurotransmitter release, and elevated brain histamine disrupts sleep, worsens anxiety, and heightens stress perception), which in turn drives more stress and further mast cell activation

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however, this theory has been called into question as APAP-protein adducts have been detected at 1 hour after APAP treatment, a time that that would precede GSH depletion

Br J Pharmacol 158:395412

Caspase 3 substrate Ac-DEVD-AMC was purchased from Enzo Life Sciences (Brussels, Belgium)