Severely reduced antioxidant and impaired mitochondrial biomarkers could be linked to post-tuberculosis lung disease in a cohort from South Africa

Background: Post-tuberculosis lung disease (PTLD) refers to unresolved lung damage and impaired lung function after successful treatment of tuberculosis (TB). Its pathogenesis is not fully understood, and we hypothesised that antioxidant-oxidant and mitochondrial factors may be instrumental. Objectives: To investigate the involvement of mitochondrial and antioxidant-oxidant biomarkers in TB patients who had had more than one previous TB episode and were in the post-TB stage of disease. Methods: Enzyme-linked immunosorbent assays were conducted on patient serum. Results: Lipid peroxidation (measured with the thiobarbituric acid reactive substances assay) was within the normal range. In contrast, the mitochondrial regulator metallothionein-1 was 240 times lower, catalase activity 7.5 times lower, and superoxide dismutase activity 273 times lower than the normal ranges for these markers. Hypoxia-inducible factor-1-alpha (HIF-1α) was below the limit of detection. The mitochondrial markers were similar across the stratified groups after stratifying the patients based on the number of previous TB episodes. Age positively correlated with the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'), a marker of left ventricular filling pressure, and it marginally correlated with pulmonary artery systolic pressure, while there were no other notable correlations. Conclusion: Our data demonstrate that antioxidant enzyme activities are extremely low in post-TB patients. A key mitochondrial protein, HIF-1α, showed no role in this context, which could suggest that these patients are not hypoxic. A novel contributor to PTLD could therefore be a limitation of antioxidant capacity and mitochondrial pathways, which is not linked to the number of previous TB episodes but may highlight the need to consider antioxidant therapy during the post-TB stage. Further research is warranted. Study synopsis: This study will allow for a better follow-up management plan of patients after resolution of TB symptoms, in order to prevent post-TB lung impairment.