N-Acetyl Cysteine as an Adjunct in the Treatment of Tuberculosis.

Dawit A Ejigu,Solomon M Abay

doi:10.1155/2020/5907839

Abstract

Oxidative stress is a common feature of tuberculosis (TB), and persons with reduced antioxidants are at more risk of TB. TB patients with relatively severe oxidative stress had also more advanced disease as measured by the Karnofsky performance index. Since adverse effects from anti-TB drugs are also mediated by free radicals, TB patients are prone to side effects, such as hearing loss. In previous articles, researchers appealed for clinical trials aiming at evaluating N-acetyl cysteine (NAC) in attenuating the dreaded hearing loss during multidrug-resistant TB (MDR-TB) treatment. However, before embarking on such trials, considerations of NAC's overall impact on TB treatment are crucial. Unfortunately, such a comprehensive report on NAC is missing in the literature and this manuscript reviews the broader effect of NAC on TB treatment. This paper discusses NAC's effect on mycobacterial clearance, hearing loss, drug-induced liver injury, and its interaction with anti-TB drugs. Based on the evidence accrued to date, NAC appears to have various beneficial effects on TB treatment. However, despite the favorable interaction between NAC and first-line anti-TB drugs, the interaction between the antioxidant and some of the second-line anti-TB drugs needs further investigations.

Highlights

Oxidative stress is a common feature of tuberculosis (TB) [1] and is evidenced by elevated lipid peroxidation products such as malondialdehyde (MDA) as well as reduced antioxidant capacity
Drug-induced liver injury (DILI) [5] and hearing loss [6] are some of these untoward effects that follow treatment with anti-TB drugs, and both adverse effects are believed to be mediated through oxidative stress
Researchers previously appealed for clinical trials aiming at evaluating N-acetyl cysteine (NAC) in attenuating hearing loss in multidrug-resistant TB (MDR-TB) patients owing to the gravity of the problem [7, 8]

Summary

Introductions

Oxidative stress is a common feature of tuberculosis (TB) [1] and is evidenced by elevated lipid peroxidation products such as malondialdehyde (MDA) as well as reduced antioxidant capacity. After successful treatment with anti-TB drugs, the elevated oxidative stress in TB patients returns to normal [1]. Anti-TB drugs induce several adverse effects in TB patients, and oxidative stress is implicated in mediating these adverse effects. Drug-induced liver injury (DILI) [5] and hearing loss [6] are some of these untoward effects that follow treatment with anti-TB drugs, and both adverse effects are believed to be mediated through oxidative stress. Antioxidants could potentially mitigate adverse effects induced by anti-TB drugs and facilitate recovery from TB. Before testing NAC in TB patients for its hearing loss protective effect, considerations of how NAC would impact other aspects of TB treatment are critical. This paper discusses NAC’s effect on mycobacterial clearance, hearing loss, and DILI as well as the antioxidant’s interaction with anti-TB drugs. The safety of NAC itself is not covered here as it has been reviewed elsewhere [7]

Antimycobacterial Properties of N-Acetyl Cysteine

Protective Effects of NAC against Ototoxicity

Protective Effect of NAC against DILI

Findings

Conclusions