02402nas a2200241   4500000000100000008004100001260000900042100001700051700001400068700001500082700002200097700001500119700001400134700001600148700001600164700001600180245009300196856007700289300001100366490000600377520176300383022001402146       2014                            d  c20141 aSchalcher TR1 aBorges RS1 aColeman MD1 aBatista Júnior J1 aSalgado CG1 aVieira JL1 aRomão PR T1 aOliveira FR1 aMonteiro MC00aClinical oxidative stress during leprosy multidrug therapy: impact of dapsone oxidation.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899049/pdf/pone.0085712.pdf  ae857120 v93 aThis study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.  a1932-6203