Metronidazole's selective toxicity for anaerobic organisms depends on which intracellular activation step?

• A Aerobic oxidation by cytochrome P450 to a toxic epoxide intermediate
• B Conversion to reactive oxygen species by anaerobic superoxide dismutase
• C Reductive activation by low-redox ferredoxin/PFOR system in anaerobes, generating nitro radical anions that damage DNA ✓
• D Hydrolysis by anaerobic beta-lactamase into an active nitroso compound

Explanation

In anaerobic organisms (and some parasites like Trichomonas, Giardia, E. histolytica), metronidazole enters the cell and is reduced by the electron-transport protein ferredoxin (linked to pyruvate-ferredoxin oxidoreductase, PFOR), generating cytotoxic nitro radical anions that alkylate and strand-break DNA, causing cell death. This activation cannot occur in aerobic cells (no equivalent low-redox ferredoxin), explaining metronidazole's selective toxicity. Mammalian and aerobic organisms lack the requisite low redox potential for this activation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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