Unveiling the molecular toxicity of Isoniazid and Rifampicin in tuberculosis therapy: emerging insights and therapeutic strategies.

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, persists as a significant worldwide health issue, resulting in millions of infections and fatalities each year. Treatment predominantly depends on first-line antibiotics, including Isoniazid (INH) and Rifampicin (RIF). Nevertheless, extended use of these medications is linked to considerable adverse effects, leading to various organ toxicities, especially hepatotoxicity and nephrotoxicity. INH causes liver and kidney damage by pathways that include oxidative stress, mitochondrial malfunction, and inflammation. RIF induces organ damage by blocking drug-metabolizing enzymes, facilitating lipid peroxidation, and triggering apoptosis and cholestasis. Although both medications are crucial in TB treatment, their synergistic effect on organ damage remains little comprehended. RIF is recognized for exacerbating INH-induced hepatic damage by increasing CYP2E1 metabolism, indicating intricate interactions. This study analyses the molecular toxicity processes generated by INH and RIF, summarizes current clinical and experimental data, and investigates the preventive potential of natural substances, such as antioxidants and phytochemicals. It also explores alternative treatment techniques, nanobiotechnology designed to mitigate drug-induced organ toxicity by giving protective agents at the same time and targeting specific mechanisms. This review presents an innovative viewpoint on the management of INH and RIF toxicity and underscores potential avenues for further research.