Changes in nitric oxide synthase and nitrite and nitrate serum levels in patients with or without mdr-tb undergoing the intensive phase of anti-tuberculosis therapy

Abstract

Aims and objectives. There is a paucity of published data on the effect of TB chemotherapy on nitric oxide (NO) synthesis and metabolism in newly diagnosed and relapsed patients with or without multi-drug resistant TB(MDR-TB). Methods. The pattern of NO response in 140 patients with pulmonary TB, including 74 with MDR-TB (1stgroup) and 66 without MDR-TB (2ndgroup) has been studied and compared to the NO status of 30 healthy donors (3rdgroup). Patients comprised those with newly diagnosed TB (NDPTB)(Subgroups 1B,2B) and recurrent or relapsed TB(Subgroup 1A,2A). The NO status was assessed by measuring inducible NO synthase (iNOS), nitrites and nitrates levels. This was measured prior to treatment initiation and two months after the prescribed chemotherapy. Results. Increased levels of NO indices were found in patients with TB when compared (1st group (iNOS-231.6±6.65pmole/min/mgB, nitrites-5.626±0.15μmol/L and nitrates-62.89±1.42μmol/L) Subgroups 1A(iNOS-208.40±8.26pmole/min/mgB, nitrites-5.027±0.17μmol/L and nitrates-59.29±1.79μmol/L) and Subgroups 1B(iNOS-260.4±8.56pmole/min/mgB, nitrites-6.371±0.19μmol/L and nitrates- 67.36±2.03μmol/L)) and 2nd group (iNOS-286.3±5.92pmole/min/mgB, nitrites-6.747±0.17μmol/L and nitrates-72.02±1.43μmol/L) Subgroups 2A(iNOS-260.9±14.12pmole/min/mgB, nitrites-5.686±0.20 μmol/L and nitrates-66.26±1.89μmol/L) and Subgroups 2B (iNOS-293.7±6.13pmole/min/mgB, nitrites-7.059±0.19μmol/L and nitrates-73.72±1.71μmol/L))) to healthy controls (iNOS-81.03±2.36 pmole/min/mgB, nitrites-3.83±0.093μmol/L and nitrates- 37.98±1.30μmol/L). After two months of chemotherapy a significant decrease in NO indicators was observed in the patients with TB, particularly in those without MDR-TB(1st group (iNOS-114.9±3.2 pmole/min/mgB, nitrites-4.21±0.13μmol/L and nitrates-46.65±1.04μmol/L) Subgroups 1A(iNOS-125.3±4.5pmole/min/mgB, nitrites-4.42±0.14μmol/L and nitrates-49.38±1.30μmol/L) and Subgroups 1B(iNOS-102±3.53pmole/min/mgB, nitrites-3.93±0.13μmol/L and nitrates-43.26±1.50μmol/L)) and 2nd group (iNOS-91.4±2.53 pmole/min/mgB, nitrites-3.67±0.09 μmol/L and nitrates-35.65±1.06μmol/L) Subgroups 2A(iNOS-106.7±5.2pmole/min/mgB, nitrites-4.04±0.19 μmol/L and nitrates-40.53±1.83 μmol/L) and Subgroups 2B(iNOS-86.7±2.59 pmole/min/mgB, nitrites-3.56±0.1μmol/L and nitrates-34.22±1.19μmol/L))).The decline in NO activity was less prominent in patients with recurrent TB and MDR-TB, which suggests lower level of immunologic and reparative processes in such patients. Conclusion.In patients with pulmonary TB, significantly higher levels of NO activity were observed as compared with the levels in healthy individuals. In patients with recurrent TB and MDRTB, significantly lower levels of NO indicators were observed by comparison with patients with newly diagnosed pulmonary TB. After two months on chemotherapy, a significant decrease in iNOS activity and NO metabolites was observed in patients with pulmonary TB, but the decrease of NO indicators was manifested mostly in the NDPTB patients and patients without MDR-TB as opposed to patients with recurrent TB and MDR-TB, which suggests lower levels of immunologic and reparative processes in such patients. Therefore, the levels of nitrites and nitrates aswell as iNOS activity may serve as additional diagnostic criteria to differentiate MDR-TB from non-resistant TB in patients with relapsed and newly diagnosed TB. Easily assessed NO-related markers can also serve as predictors of treatment outcome since patients with drug-susceptible strains had lower NO output approaching levels found in controls.