Oxidative Stress and First-Line Antituberculosis Drug-Induced Hepatotoxicity

Area of Science:

• Pharmacology
• Toxicology
• Hepatology

Background:

• Hepatotoxicity from antituberculosis drugs is a significant clinical concern.
• This toxicity can negatively impact tuberculosis treatment outcomes.
• Oxidative stress and mitochondrial dysfunction are implicated in drug-induced liver injury.

Purpose of the Study:

• To review the role of oxidative stress and mitochondrial dysfunction in antituberculosis drug-induced hepatotoxicity.
• To identify risk factors and potential shared pathogenetic mechanisms.
• To highlight the need for further research in prediction, prevention, and treatment.

Main Methods:

• Literature review focusing on first-line antituberculosis drugs.
• Analysis of existing data on risk factors and molecular mechanisms.
• Synthesis of information regarding oxidative stress, redox homeostasis, and mitochondrial function.

Main Results:

• Oxidative stress and mitochondrial dysfunction are key contributors to antituberculosis drug-induced hepatotoxicity.
• Identified risk factors (e.g., age, malnutrition, viral hepatitis, HIV) are often associated with increased oxidative stress.
• Disease-drug interactions may share common pathogenetic pathways for liver injury.

Conclusions:

• Antituberculosis drug-induced hepatotoxicity is linked to oxidative stress and mitochondrial dysfunction.
• Further translational and clinical research is crucial for understanding pathogenesis and developing effective therapies, including antioxidants and pharmacogenetics.
• Current management strategies are limited, emphasizing the need for novel approaches.