Clofazimine's bactericidal effect against M. leprae involves generation of reactive oxygen species. The mechanism involves which electron transfer pathway?

• A Clofazimine inhibits mycobacterial catalase, allowing endogenous H2O2 to accumulate
• B Clofazimine chelates iron and uses the Fenton reaction to produce hydroxyl radicals
• C Clofazimine accepts electrons from NADH and donates them to oxygen, generating superoxide and H2O2 via futile redox cycling ✓
• D Clofazimine stimulates host macrophage NADPH oxidase (respiratory burst) activity

Explanation

Clofazimine is a phenazine dye that undergoes a redox cycle within mycobacteria. It accepts electrons from NADH (via NADH dehydrogenase/NDH-2 in M. tuberculosis and likely similar enzymes in M. leprae), becoming reduced to a semiquinone radical. This reduced form then donates electrons to molecular oxygen, regenerating the oxidised clofazimine while producing superoxide anion (O2•-) and subsequently hydrogen peroxide (H2O2). This futile redox cycling depletes NADH, disrupts the electron transport chain, and the accumulating reactive oxygen species cause lethal oxidative damage. This accounts for clofazimine's activity against dapsone-resistant M. leprae and its use in MDR-TB regimens.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.