Emna Gaies, Nadia Jebabli, Sameh Trabelsi, Issam Salouage, Rim Charfi, Mohamed Lakhal and Anis Klouz
Methotrexate (MTX) is an antifolate first developed to treat certain types of cancer. It was used at higher doses as a cancer therapy and since 1990 it is used at much lower doses to treat rheumatic diseases . Side effects of MTX high dose (MTX-HD) may be life threatening, however those of various doses of oral MTX are variable because of the interindividual variability of gastrointestinal absorption of this drug. Bone marrow, gastrointestinal mucosa and hair are particularly vulnerable to the effects of MTX, secondary to their high rate of cellular turnover  and because MTX concentration is inversly proportianal to renal clearance , renal toxicity is frequent with MTX-HD. This review aimed at exposing MTX toxicity in different organs, at explaining pathogenic mechanisms of these toxicities and their prevention or treatment.