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

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.

• Authors: Judit Marsillach, Natàlia Ferré, Jordi Camps, Francesc Riu, Anna Rull, Jorge Joven
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 233 Issue 1 Pg. 38-47 (Jan 2008) ISSN: 1535-3702 [Print] England
• PMID: 18156304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Folic Acid
• Carbon Tetrachloride

Topics

• Animals
• Apoptosis (drug effects)
• Carbon Tetrachloride
• Folic Acid (administration & dosage, toxicity)
• Gene Expression Regulation (drug effects)
• Lipid Peroxidation
• Liver (drug effects)
• Liver Cirrhosis, Experimental (chemically induced, genetics, pathology)
• Male
• Rats
• Rats, Wistar