{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T18:00:37Z","timestamp":1782410437250,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,11,12]],"date-time":"2001-11-12T00:00:00Z","timestamp":1005523200000},"content-version":"vor","delay-in-days":195,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The objective of this study was to investigate whether folinic acid supplementation would protect young mice against suppression of growth by methotrexate (MTX). Four equal groups of Balb\/c young male mice (5 animals in each group; mean\u00b1SD body weight 9.64\u00b10.85 g, in their rapid growth phase) were subjected to the following drug treatment: One group was given MTX (3.5 mg\/kg body weight) intraperitoneally on every 2nd day, another received folinic acid (7.0 mg\/kg body weight) intraperitoneally every 2nd day. The third group was given both of these drugs (MTX on every 2nd day and folinic acid 8 h post\u2010MTX injection). The fourth group was injected with physiological saline every other day to serve as a control group. Total body weight, food and water consumption by animals in each group were monitored every second day for a period of 3 weeks. After this period mice were sacrificed and liver, spleen and kidneys were excised, weighed and analyzed for MTX and dihydrofolate reductase activity. A small segment of the proximal part of small intestine and small pieces of liver and kidney were also removed to study morphological changes.<\/jats:p><jats:p>Compared to the groups, which received folinic acid alone, folinic acid plus MTX or physiological saline, mean increase in body weight (6.8\u00b10.8 g) of mice over a period of 3 weeks was minimal in the group receiving MTX alone (one\u2010way ANOVA <jats:italic>p<\/jats:italic>=0.0001). The mean weights of liver and kidney in this group receiving MTX alone were also found to be significantly less than the mean weights of these organs in the 3 groups (<jats:italic>p<\/jats:italic>&lt;0.001). The negative effect on growth of animals appears not only due to malabsorption but inhibition of pathway of <jats:italic>de novo<\/jats:italic> DNA synthesis may also be involved. This is supported by loss of villous pattern in small intestine of mice treated with MTX alone and increased accumulation of free MTX and decreased dihydrofolate reductase in the liver of the group receiving MTX alone as compared with the group receiving MTX plus folinic acid. The data indicate that the administration of folinic acid protects mice against suppression of growth by MTX. On the basis of these observations it can be deduced that patients suffering from juvenile rheumatoid arthritis or acute lymphoblastic leukaemia receiving MTX over a long period of time might be at a risk of experiencing short\u2010term suppression of growth, however they could benefit from supplementation with folinic acid. Copyright \u00a9 2001 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.271","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T16:22:28Z","timestamp":1030292548000},"page":"169-178","source":"Crossref","is-referenced-by-count":14,"title":["Folinic acid protects against suppression of growth by Methotrexate in mice"],"prefix":"10.1002","volume":"22","author":[{"given":"M.","family":"Perwaiz Iqbal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakhara","family":"Sultana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naseema","family":"Mehboobali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahid","family":"Pervez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,11,12]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198311033091805"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199204163261602"},{"key":"e_1_2_1_4_2","first-page":"S95","article-title":"Methotrexate safety in juvenile rheumatoid arthritis (JRA)","volume":"33","author":"Rose CD","year":"1990","journal-title":"Arthritis Rheum"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80709-7"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199204163261608"},{"key":"e_1_2_1_7_2","first-page":"53","article-title":"Low dose methotrexate in recalcitrant JRA\u2010results of the USA\u2013USSR randomized controlled trial","volume":"34","author":"Giannini EH","year":"1991","journal-title":"Arthritis Rheum"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1995.tb13540.x"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0820181"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1099-081X(199911)20:8<389::AID-BDD201>3.0.CO;2-1"},{"key":"e_1_2_1_11_2","first-page":"468","volume-title":"The Biochemistry of Folic Acid and Related Pteridines","author":"Blakley RL","year":"1969"},{"key":"e_1_2_1_12_2","first-page":"631","article-title":"Effect of folate compounds on the accumulation of methotrexate and the activity of dihydorfolate reductase in liver, kidney and small intestine of the mouse","volume":"223","author":"Rothenberg SP","year":"1982","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_13_2","first-page":"575","article-title":"Ligand\u2010binding radioassay for the antifolate compounds. 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