Prediction and Validation of Enzyme and Transporter Off-Targets for Metformin. Journal of Pharmacokinetics and Pharmacodynamics, vol
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In addition, free radicals can lead to mutation and DNA damage.[] First, it is well known that phagocytes are activated by certain pro-inflammatory mediators such as LTB4 or platelet activating factor (PAF) to release large amounts of potentially cytotoxic reactive oxygen metabolites into the interstitial compartment.[] Enhanced synthesis of LTB4 and PAF has been demonstrated in mucosal samples obtained from patients with active IBD.[] Secondly, there are several reports that have demonstrated that phagocytic leukocytes obtained from patients with active IBD respond to various proinflammatory stimuli with enhanced reactive oxygen metabolism when compared to cells obtained from healthy volunteers.[] Also, high NOS activity has been found in experimental models of colitis and in the intestinal mucosa of patients with IBD.[] High levels of the end products of NO metabolism, nitrates, and nitrites were found in the plasma, feces, and colonic lumen of IBD patients.[] It seems that a dramatic increase of oxygen consumption can be observed during proinflammatory agent's interaction with neutrophil-specific receptors [Figure 2]
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