Moderately high folic acid supplementation exacerbates experimentally induced liver fibrosis in rats.

@article{citeulike:2799139, abstract = {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(4)-treated rats and (ii) the influence of folic acid supplements on the hepatic recovery following the interruption of the CCl(4)-induced toxic injury. Four experimental groups of rats were used: CCl(4)-treated rats (0.5 ml of CCl(4) twice a week i.p.) 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(4) 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(4)-treated rats. Follow-up studies are needed to determine whether folic acid treatment would be contraindicated in patients with chronic liver diseases.}, address = {Centre de Recerca Biom\`{e}dica, Hospital Universitari de Sant Joan, Institut de Recerca en Ci\`{e}ncies de la Salut, Reus, Spain.}, author = {Marsillach, J. and Ferr\'{e}, N. and Camps, J. and Riu, F. and Rull, A. and Joven, J. }, citeulike-article-id = {2799139}, doi = {10.3181/0703-RM-59}, issn = {1535-3702}, journal = {Experimental biology and medicine (Maywood, N.J.)}, month = {January}, number = {1}, pages = {38--47}, posted-at = {2008-05-14 16:10:52}, priority = {2}, title = {Moderately high folic acid supplementation exacerbates experimentally induced liver fibrosis in rats.}, url = {http://dx.doi.org/10.3181/0703-RM-59}, volume = {233}, year = {2008} }

TY - JOUR ID - citeulike:2799139 L3 - citeulike-article-id:2799139 TI - Moderately high folic acid supplementation exacerbates experimentally induced liver fibrosis in rats. JF - Experimental biology and medicine (Maywood, N.J.) VL - 233 IS - 1 SP - 38 EP - 47 AD - Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut de Recerca en Ciències de la Salut, Reus, Spain. SN - 1535-3702 N2 - 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(4)-treated rats and (ii) the influence of folic acid supplements on the hepatic recovery following the interruption of the CCl(4)-induced toxic injury. Four experimental groups of rats were used: CCl(4)-treated rats (0.5 ml of CCl(4) twice a week i.p.) 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(4) 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(4)-treated rats. Follow-up studies are needed to determine whether folic acid treatment would be contraindicated in patients with chronic liver diseases. AU - Marsillach, J AU - Ferré, N AU - Camps, J AU - Riu, F AU - Rull, A AU - Joven, J PY - 2008/01// UR - http://dx.doi.org/10.3181/0703-RM-59 ER -