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Introduction Methotrexate (MTX) is an antineoplastic agent widely used in low dose to treat patients with rheumatoid arthritis (RA). Its side effects can partly be explained by folate antagonism. Folinic acid (Leucovorin) is generally administered with MTX to decrease MTX-induced toxicity. However information regarding the inhibitory effect of folinic acid against cytogenetic damage caused by MTX is limited. The aim of this study was to assess the protective effect of folinic acid against MTX-genotoxicity. Methods This study was done on Wistar albino rats and in patients with RA. Forty rats of both sexes were randomized into four equal groups and dosed in the following way: Group-I, distilled water vehicle; Group-II, 0.5mg/kg folinic acid; Group-III, 0.5 mg/kg MTX; Group-IV, 0.5mg/kg folinic acid plus 0.5mg/kg MTX. Doses were given i.p., once daily for 8 consecutive days. A bone marrow chromosomal study and a …