Oxidative stress and its impact on mitochondrial DNA in pulmonary tuberculosis patients- a pilot study

Pulmonary tuberculosis (PTB) remains a major cause of morbidity and mortality all around the world. Recent studies have pointed out increased oxidative stress and also DNA damage in peripheral blood in PTB. Till date, to the best of our knowledge, no study has so far been conducted to show the mitochondrial DNA (mtDNA) deletions mapping in PTB patients. Therefore we performed the present study with the aim to investigate oxidative stress parameters along with mtDNA damage in newly diagnosed untreated PTB patients.

This is a prospective study carried out in Mahatma Gandhi Institute of Medical Sciences, Sevagram,Wardha, Maharashtra during september 2017 to september 2018.Thirty newly diagnosed untreated PTB patients and thirty age matched healthy controls were enrolled in the present study. Analysis of Oxidative stress parameters such as nitric oxide (NO) and malondialdehyde (MDA) were done by calorimetric methods. Assessment of mitochondrial DNA damage was carried out by mtDNA deletions mapping using primer shift long range polymerase chain reaction technique.

There was significant increase in levels of oxidative stress parameters, nitric oxide and malondialdehyde, in PTB patients compared to controls (p < 0.01). Generally there are two common deletion sites of "13 bp direct repeats" (ACCTCCCTCACCA) in mtDNA. One at the junction sites from bp 8470 to 8482 bp and another from bp 13447 to 13460 bp which make mtDNA more prone for 4977bp deletion. Out of thirty cases of PTB, two cases showed mtDNA damage in the form of mtDNA deletion of 4977bp. There was no mtDNA deletion in any control which can be attributed to continuous generation of oxidative stress.

This pilot study has been able to demonstrate that compared to controls, in newly diagnosed pulmonary tuberculosis patients some mtDNA damage did occur and was probably due to continuous generation of oxidative stress in tuberculous patients. However, sample size is too small to draw any conclusions but definitely a more comprehensive study, by recruiting more number of pulmonary tuberculosis patients is warranted to establish correlation between oxidative stress and mtDNA damage in PTB.