{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:42:06Z","timestamp":1777873326640,"version":"3.51.4"},"reference-count":48,"publisher":"Frontiers Media SA","issue":"1","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p>\n                    Under certain clinical circumstances, folic acid can have undesirable effects. We investigated the following: (i) the effects of moderately high folic acid supplementation on the course of liver impairment in CCl\n                    <jats:sub>4<\/jats:sub>\n                    -treated rats and (ii) the influence of folic acid supplements on the hepatic recovery following the interruption of the CCl\n                    <jats:sub>4<\/jats:sub>\n                    -induced toxic injury. Four experimental groups of rats were used: CCl\n                    <jats:sub>4<\/jats:sub>\n                    -treated rats (0.5 ml of CCl\n                    <jats:sub>4<\/jats:sub>\n                    twice a week ip) fed standard chow for up to 12 weeks (Group A); treated rats fed chow supplemented with 25 mg\/kg folic acid from weeks 6 to 12 (Group B); treated rats fed a standard diet but with CCl\n                    <jats:sub>4<\/jats:sub>\n                    discontinued after 6 weeks to allow for tissue recovery over 4 weeks (Group C); rats as Group C but fed a diet supplemented with 25 mg\/kg folic acid from weeks 6 to 10 (Group D). Liver and blood samples were obtained for biochemical, histological, and gene expression analyses. Animals that received the supplement had a higher content of collagen, activated stellate cells, and apoptotic parenchymal cells in biopsy tissue at weeks 8 and 10 of treatment and more extensive alterations in serum albumin and bilirubin concentrations (Group B vs. Group A). In some of the time periods analyzed, alterations were observed in the expression of genes related to apoptosis (B-cell leukemia\/lymphoma 2, inhibitor of apoptosis 2) and to fibrosis (procollagen I, matrix metalloproteinase 7). In the recovery period (Groups C and D), folic acid administration was associated with increased hepatic inflammation and apoptosis and with a decrease in the tissue inhibitor of metalloproteinase-3 expression following 1 week of recovery. We conclude that folic acid administration aggravates the development of fibrosis in CCl\n                    <jats:sub>4<\/jats:sub>\n                    -treated rats. Follow-up studies are needed to determine whether folic acid treatment would be contraindicated in patients with chronic liver diseases.\n                  <\/jats:p>","DOI":"10.3181\/0703-rm-59","type":"journal-article","created":{"date-parts":[[2008,5,12]],"date-time":"2008-05-12T19:11:21Z","timestamp":1210619481000},"page":"38-47","source":"Crossref","is-referenced-by-count":13,"title":["Moderately High Folic Acid Supplementation Exacerbates Experimentally Induced Liver Fibrosis in Rats"],"prefix":"10.3389","volume":"233","author":[{"given":"Judit","family":"Marsillach","sequence":"first","affiliation":[{"name":"Centre de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut de Recerca en Ci\u00e8ncies de la Salut, Reus, Spain; Department of Clinical Biochemistry and Molecular Genetics, Hospital Cl\u00ednic Universitari, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nat\u00e0lia","family":"Ferr\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut de Recerca en Ci\u00e8ncies de la Salut, Reus, Spain; Department of Clinical Biochemistry and Molecular Genetics, Hospital Cl\u00ednic Universitari, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Camps","sequence":"additional","affiliation":[{"name":"Centre de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut de Recerca en Ci\u00e8ncies de la Salut, Reus, Spain; Department of Clinical Biochemistry and Molecular Genetics, Hospital Cl\u00ednic Universitari, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesc","family":"Riu","sequence":"additional","affiliation":[{"name":"Centre de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut de Recerca en Ci\u00e8ncies de la Salut, Reus, Spain; Department of Clinical Biochemistry and Molecular Genetics, Hospital Cl\u00ednic Universitari, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Rull","sequence":"additional","affiliation":[{"name":"Centre de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut de Recerca en Ci\u00e8ncies de la Salut, Reus, Spain; Department of Clinical Biochemistry and Molecular Genetics, Hospital Cl\u00ednic Universitari, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Joven","sequence":"additional","affiliation":[{"name":"Centre de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut de Recerca en Ci\u00e8ncies de la Salut, Reus, Spain; Department of Clinical Biochemistry and Molecular Genetics, Hospital Cl\u00ednic Universitari, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2008,1,1]]},"reference":[{"key":"bibr-R1","unstructured":"Crott JW, Mashiyama ST, Ames BN, Fenech M. The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes\n                      in vitro\n                      . Cancer Epidemiol Biomarkers Prev 10: 1089\u20131096, 2001."},{"key":"bibr-R2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.7.3290"},{"key":"bibr-R3","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.12.14.1491"},{"key":"bibr-R4","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/65.1.46"},{"key":"bibr-R5","doi-asserted-by":"publisher","DOI":"10.1177\/153537020422901002"},{"key":"bibr-R6","unstructured":"Food and Drug Administration. Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid. Final rule. 21 CFR Parts 136, 137, and 139, Fed Regist 61: 8781\u20138807, 1996."},{"key":"bibr-R7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.23.2981"},{"key":"bibr-R8","doi-asserted-by":"publisher","DOI":"10.1177\/153537020122600402"},{"key":"bibr-R12","doi-asserted-by":"publisher","DOI":"10.1136\/gut.39.5.732"},{"key":"bibr-R13","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.085480"},{"key":"bibr-R14","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-2863(98)00074-6"},{"key":"bibr-R15","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/133.11.3731S"},{"key":"bibr-R16","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.8.2413S"},{"key":"bibr-R17","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i11.1571"},{"key":"bibr-R19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2005.11.004"},{"key":"bibr-R20","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80218-9"},{"key":"bibr-R21","unstructured":"Neuman MG. Cytokines\u2014central factors in alcoholic liver disease. 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Short term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations. Lipids 36:S27\u2013S32, 2002.","DOI":"10.1007\/s11745-001-0678-8"},{"key":"bibr-R45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.24.14313"},{"key":"bibr-R46","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01031-X"},{"key":"bibr-R47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26052"},{"key":"bibr-R48","doi-asserted-by":"publisher","DOI":"10.1038\/ng1413"},{"key":"bibr-R49","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.5.1130"},{"key":"bibr-R50","doi-asserted-by":"crossref","unstructured":"Woo CWH, Prathapasinghe GA, Siow YL, Karmin O. Hyperhomocysteinemia induces liver injury in rat: protective effect of folic acid supplementation. 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