DISCUSSION
Tuberculosis is major public health problem worldwide [21]. It is
estimated that approximately one-third of the world’s population is
living with latent TB. Until recent years, it remains as one of the most
important causes of death. Therefore, biomarkers are very important for
effective and accurate determinations in the diagnosis, treatment
monitoring and result of tuberculosis disease. The currently available
diagnostic technology for TB detection is inadequate. Novel biomarkers
are needed in the prognosis and treatment process of the disease
[22].
Free radical production has been described in different cancers, lung
injury and pulmonary emphysema [23-26]. Also degenerative lung
diseases such as tuberculosis are associated with lung
oxidant-antioxidant imbalance [27]. Mycobacterium tuberculosis is
intracellular pathogens, which grow and replicate in the host
macrophages. It is well known that macrophages undergo respiratory burst
after contact with this microorganism. Increased amounts of ROS are
produced as a result of respiratory burst. ROS released from macrophages
cause tissue damage in respiratory tract infections [23]. Containing
sulfurous amino acid molecules are more sensitive to free radicals. The
sulphurous amino acids cysteine and cystine are also sensitive to free
radical attack. Proteins with a large number of disulfide bonds such as
IgG and albumin break down their three-dimensional structure. Thus, they
can not perform their normal functions. Changes in protein structure can
lead to changes in antigenicity and proteolysis. Radicals can react with
membrane proteins and cause impairment of the functions of enzyme,
neurotransmitter and receptor proteins [28, 29].
The plasma thiol pool mainly comprises albumin thiols and protein
thiols, smaller amounts of low-molecular-weight thiols such as cysteine
(Cys), cysteinyl glycine, homocysteine, glutathione, and γ-glutamyl
Cys [12]. Measuring plasma total thiol levels and defining thiol /
disulfide homeostasis is a good indicator of excessive free radical
formation in many diseases. it also provides important information about
the extent of free radical-mediated oxidation that causes protein damage
[14, 30].
Erel and Neselioğlu reported higher plasma disulfide levels in
degenerative diseases such as obesity, pneumonia, bronchiolitis and
diabetes mellitus than healthy groups; In another word, thiol /
disulfide homeostasis has shifted towards disulfide [12]. Topuz et
al. detected that serum thiol levels in acute pulmonary thromboembolism
(APE) patients were significantly low compared to a control group and
disulfide level and disulfide/total thiol ratio were higher in APE group
than control group [31]. Recent studies have shown that the
thiol/disulphide homeostasis is disturbed in lung diseases such as
infectious pneumonia [32], obstructive sleep apnea syndrome
[33], COPD, asthma [34] and silicasis [35]. Plasma total
thiol levels are reduced in patients with COPD or asthma [36]. Solak
et al have found NT and TT levels significantly lower in smokers in
comparison with the control group [37]. In a previous study, serum
SOD activities were significantly decreased in tuberculosis patients
compared to healthy controls, and serum MDA levels were increased [38,
39]. This result indicates that oxidative stress is increased in
patients with lung tuberculosis. Durak et al. investigated pleural fluid
and serum superoxide dismutase (SOD) values in patients with lung
cancer, tuberculosis and heart failure, and found that pleural fluid and
serum SOD values of all patient groups, being the highest in the
tuberculosis group, were higher than the control group values. As a
result, they stated that this enzyme activity could be used as a
nonspecific prognostic indicator in detecting cellular and mitochondrial
tissue damage [24].
Limited data is available on the relationshipbetween thiol/disulphide
homeostasis and lung diseases. Determination of dynamic thiol/disulphide
status in diseases where oxidative stress plays a major role in
pathogenesis would be important. There has been no report about thiol
levels in lung tuberculosis patients, so far. To our knowledge, this
study is the first study that investigates thiols and thiol/disulphide
homeostasis in patients with lung tuberculosis. In this study, we found
that native and total thiol levels were significantly decreased in
patients with lung tuberculosis. We think that the ROS released from the
increased macrophages in lung tuberculosis patients decrease the thiol
levels by oxidizing the thiols. In this study, disulfide/native thiol
and disulfide/total thiol levels were found to be higher in lung
tuberculosis patients when compared with the control group. However,
disulfide levels were higher in the control group than in the patient
group.