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Moreover, some compounds may undergo bioactivation during Phase I metabolism, forming reactive intermediates that can cause adverse effects or contribute to toxicity

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This evidence might suggest the additional specific points to be considered for the demonstrated spontaneous release of NO [49,67,68], activated phosphorilazation of eNOS [61], counteraction of the adverse effect of NOS-blockade (i.e., L-NAME hypertension and pro-thrombotic effect), and counteraction of the adverse effect of NOS overstimulation (i.e., L-arginine hypertension and anti-thrombotic effect) [49,67,69]

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