Protective effect of folinic acid on low-dose methotrexate genotoxicity

Introduction Methotrexate (MTX) is an antineoplastic agent widely used in l ow 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 i nformation regarding the inhibitory effect of folinic acid against cytogene tic damage caused by MTX is limited. The aim of this study was to assess th e 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 followi ng way: Group-I, distilled water vehicle; Group-II, 0.5 mg/kg folinic acid; Group-III, 0.5 mg/kg MTX; Group-IV, 0.5 mg/kg folinic acid plus 0.5 mg/kg MTX. Doses were given i.p., once daily for 8 consecutive days. a bone marro w chromosome study and a micronucleus test were performed for each rat. Twenty patients with RA (5 males and 15 females) on a 10 mg weekly dose of MTX, i.m., for one month, were administered the same dose of MTX in additio n to 10 mg of folinic acid as a single dose 4 hours after MTX administratio n, i.m., every week for another 4 weeks. Chromosomal studies as well as a m icronucleus test were evaluated for each patient. Results MTX produced a si gnificant genetic injury as proved by the increased incidence of chromosoma l aberration and micronuclei formation in Group-III animals. Inversely, fol inic acid (group IV) produced a significant protection against genetic dama ges induced by MTX. In RA patients, folinic acid provides satisfactory impr ovement of MTX-induced genetic damage. Conclusion folinic acid has a protec tive affect against MTX genotoxicity in human as well as in animal models.