RGD Reference Report - Moderately high folic acid supplementation exacerbates experimentally induced liver fibrosis in rats. - Rat Genome Database
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Moderately high folic acid supplementation exacerbates experimentally induced liver fibrosis in rats.

Authors: Marsillach, J  Ferre, N  Camps, J  Riu, F  Rull, A  Joven, J 
Citation: Marsillach J, etal., Exp Biol Med (Maywood). 2008 Jan;233(1):38-47.
RGD ID: 2290422
Pubmed: (View Article at PubMed) PMID:18156304
DOI: Full-text: DOI:10.3181/0703-RM-59

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.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Bcl2  (BCL2, apoptosis regulator)
Timp3  (TIMP metallopeptidase inhibitor 3)


Additional Information