Final answer:
Chronic methotrexate therapy can lead to folate deficiency which is best treated with folinic acid (leucovorin) to replenish the necessary tetrahydrofolic acid for DNA synthesis.
Step-by-step explanation:
Chronic methotrexate therapy that results in folate depletion is best treated with folinic acid (leucovorin).
Methotrexate inhibits the enzyme responsible for converting folic acid to tetrahydrofolic acid, which is crucial for DNA synthesis. This inhibition leads to reduced production of the coenzymes needed for one-carbon transfer reactions essential not only for the biosynthesis of purines but also for the synthesis of pyrimidines, subsequently affecting the cell cycle and division. Prolonged methotrexate use can cause folate deficiency, as folic acid cannot be adequately converted to its active form.
To counteract this, folinic acid is administered, which bypasses the inhibited step caused by methotrexate and directly replenishes the reduced form of folic acid needed for cell processes. The use of folinic acid is specifically critical in avoiding the development of megaloblastic anemia, which presents symptoms such as glossitis and G.I tract disturbances. Additionally, it's important to note that folinic acid is also used in the treatment of neurotoxoplasmosis and other conditions where reduced folate levels are evident.