Leucovorin rescue is used to rescue host cells when methotrexate is used.

• A. Leucovorin rescue
• B. Protamine sulfate
• C. Naloxone
• D. Vitamin K

Answer: (A)

Leucovorin rescue works by providing a form of folate that bypasses the block caused by methotrexate. Methotrexate inhibits the enzyme dihydrofolate reductase, which blocks the conversion of dihydrofolate to tetrahydrofolate. Without tetrahydrofolate, cells can’t synthesize thymidylate or purines, so DNA replication in rapidly dividing cells stops and toxicity occurs, especially in bone marrow and gut lining.

Leucovorin, also known as folinic acid, is a reduced folate that can be converted into the active folate cofactors downstream of the blocked step without needing dihydrofolate reductase. By supplying these active folate forms to normal host cells, leucovorin allows them to resume DNA synthesis and survive MTX exposure, effectively “rescuing” them. This strategy lets high-dose methotrexate do its anti-cancer job while reducing toxicity to the patient’s healthy tissues.

The other agents listed serve completely different roles: protamine sulfate reverses heparin’s effects, naloxone reverses opioid overdose, and vitamin K reverses warfarin anticoagulation. They don’t provide the folate rescue needed after methotrexate.