RESUMO
Effective control of Mycobacterium tuberculosis (Mtb) infection is mediated by multifaceted factors that involve both the endocrine and immune system. Profiling hormones and antibodies in different stages of TB provides insight in the pathogenesis of the disease. In this study, we profiled endocrine hormones (dehydroepiandrosterone (DHEA), cortisol, testosterone, estradiol, growth hormone and leptins) and Mtb strain H37RV lipoarabinomannan (LAM)-specific antibody levels in plasma samples, collected from pulmonary TB (PTB) patients, TB lymphadenitis (TBLN) patients and latently infected (QFT-positive) or uninfected (QFT-negative) apparently healthy individuals using ELISA. Plasma levels of leptin and DHEA were significantly low in PTB and TBLN patients compared to healthy controls (P<0.0001 and P=0.02, respectively), whereas these levels significantly increased following anti-TB treatment (P=0.002 and P=0.0001, respectively) among TB patients. The levels of estradiol and testosterone significantly improved following anti-TB treatment (P=0.03 and P=0.0003, respectively), whereas cortisol and growth hormones declined significantly (P <0.05). Similarly, LAM-specific IgG, IgM and IgA were significantly higher in PTB patients compared to other groups, whereas levels of IgG1 subtype were significantly higher among LTBI groups compared to both TB patients and QFT-negative individuals (P<0.0001). Overall, we observed significantly variable levels of endocrine hormones as well as immunoglobulins across the spectrum of TB illness and such profiling has a significant contribution in selection of effective biomarkers that have roles in TB treatment monitoring or diagnostics. Although this study did not show a functional association between hormones and antibodies, alterations in the levels of these biomarkers suggest the key roles these markers play in TB pathogenesis.
Assuntos
Tuberculose Pulmonar , Tuberculose , Formação de Anticorpos , Biomarcadores , Desidroepiandrosterona , Estradiol , Humanos , Hidrocortisona , TestosteronaRESUMO
The objective of this study was to evaluate the association between exposure to heavy metals and oxidative DNA damage among residents living in the potentially more polluted downstream (Akaki-Kality) area of Addis Ababa, in comparison to the upstream area (Gullele). For this, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was used as a biomarker for oxidative DNA damage and heavy metals (Fe, Zn, Mn, Cu, Ni, Cr, Pb, As) as indicators of exposure. The concentrations of heavy metals in nails were determined using inductively coupled plasma optical emission spectroscopy (ICP-OES), and 8-OHdG in urine using Enzyme-Linked with Immunosorbent Assay (ELISA), from 95 residents of the two areas, upstream and downstream. The urinary 8-OHdG concentration was not significantly different (p = 0.05) between the two Sub-Cities, with mean of 18.50 ± 4.37 ng/mg Creatinine in Akaki-Kality and 17.30 ± 5.83 ng/mg Creatinine in Gullele. Also, there were no statistically significant (p = 0.05) difference among the different demographic groups according to gender, age, educational status, body mass index or habit of alcohol consumption. However, the interactions of sex with age, sex with alcohol consumption and alcohol consumption with education were found to affect the urinary 8-OHdG levels of residents of the two Sub-Cities. The mean concentrations (µg/g) of the elements were 488 and 1035 for Fe, 106 and 251 for Zn, 13.0 and 31.2 for Mn, 5.23 and 6.63 for Cu, 11.2 and 7.39 for Ni, 2.23 and 2.02 for Cr, 0.09 and 0.63 for Pb; and 0.16 and 0.25 for As, in nail samples from Akaki-Kality and Gullele, respectively. The determined concentrations of the heavy metals in nails were not significantly associated (p = 0.05) with the corresponding urinary levels of 8-OHdG. Hence, the observed 8-OHdG might have been caused by environmental exposure to toxic substances other than the analyzed heavy metals.