**Question:** Drug used to counteract Methotrexate toxicity:

A. Allopurinol
B. Azathioprine
C. Leucovorin
D. Cytosine arabinoside

**Core Concept:**
Methotrexate is an antifolate drug used for the treatment of various cancers and autoimmune conditions, but can cause toxicity due to its inhibition of dihydrofolate reductase (DHFR) enzyme and depletion of folic acid. Leucovorin (folinic acid) is a synthetic form of folic acid that acts as a competitive inhibitor of DHFR, counteracting methotrexate toxicity by replenishing the folic acid levels and restoring cellular folate homeostasis.

**Why the Correct Answer is Right:**
Leucovorin (Cytosine arabinoside) is the correct answer because it is a synthetic form of folic acid that specifically inhibits DHFR. By competitively inhibiting DHFR, leucovorin prevents methotrexate from binding to the enzyme and restores cellular folate homeostasis, thereby counteracting methotrexate toxicity.

**Why Each Wrong Option is Incorrect:**

A. Allopurinol is an antigout medication that reduces uric acid production and is unrelated to methotrexate toxicity or folate restoration.

B. Azathioprine, an immunosuppressant, is unrelated to methotrexate toxicity or folate restoration.

D. Cytosine arabinoside (Ara-C) is a nucleoside analogue used in cancer chemotherapy, not related to methotrexate toxicity or folate restoration.

**Clinical Pearl:**
In cases of methotrexate toxicity, prompt administration of leucovorin is essential to minimize the severity of the toxicity and improve patient outcomes.