Methyl deficient diet aggravates experimental colitis in rats
Open Access
- 29 December 2010
- journal article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 15 (11), 2486-2497
- https://doi.org/10.1111/j.1582-4934.2010.01252.x
Abstract
Inflammatory bowel diseases (IBD) result from complex interactions between environmental and genetic factors. Low blood levels of vitamin B12 and folate and genetic variants of related target enzymes are associated with IBD risk, in population studies. To investigate the underlying mechanisms, we evaluated the effects of a methyl-deficient diet (MDD, folate, vitamin B12 and choline) in an experimental model of colitis induced by dextran sodium sulphate (DSS), in rat pups from dams subjected to the MDD during gestation and lactation. Four groups were considered (n= 12–16 per group): C DSS− (control/DSS−), D DSS− (deficient/DSS−), C DSS+ (control/DSS+) and D DSS+ (deficient/DSS+). Changes in apoptosis, oxidant stress and pro-inflammatory pathways were studied within colonic mucosa. In rat pups, the MDD produced a decreased plasma concentration of vitamin B12 and folate and an increased homocysteine (7.8 ± 0.9 versus 22.6 ± 1.2 μmol/l, P < 0.001). The DSS-induced colitis was dramatically more severe in the D DSS+ group compared with each other group, with no change in superoxide dismutase and glutathione peroxidase activity, but decreased expression of caspase-3 and Bax, and increased Bcl-2 levels. The mRNA levels of tumour necrosis factor (TNF)-α and protein levels of p38, cytosolic phospolipase A2 and cyclooxygenase 2 were significantly increased in the D DSS+ pups and were accompanied by a decrease in the protein level of tissue inhibitor of metalloproteinases (TIMP)3, a negative regulator of TNF-α. MDD may cause an overexpression of pro-inflammatory pathways, indicating an aggravating effect of folate and/or vitamin B12 deficiency in experimental IBD. These findings suggest paying attention to vitamin B12 and folate deficits, frequently reported in IBD patients.Keywords
This publication has 56 references indexed in Scilit:
- Methyl Donor Deficiency Affects Fetal Programming of Gastric Ghrelin Cell Organization and Function in the RatThe American Journal of Pathology, 2010
- Vitamin B12 deficiency reduces proliferation and promotes differentiation of neuroblastoma cells and up-regulates PP2A, proNGF, and TACEProceedings of the National Academy of Sciences of the United States of America, 2009
- Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell linesThe Journal of Nutritional Biochemistry, 2008
- Oxidative Stress, Inflammation and Neutrophil Superoxide Release in Patients with Crohn’s Disease: Distinction Between Active and Non-active DiseaseDigestive Diseases and Sciences, 2008
- Unravelling the pathogenesis of inflammatory bowel diseaseNature, 2007
- Apoptosis of T cells and the control of inflammatory bowel disease: therapeutic implicationsGut, 2007
- Low folate levels may protect against colorectal cancerGut, 2006
- Homocysteine Induces Programmed Cell Death in Human Vascular Endothelial Cells through Activation of the Unfolded Protein ResponseOnline Journal of Public Health Informatics, 2001
- Relationship between total plasma homocysteine, polymorphisms of homocysteine metabolism related enzymes, risk factors and coronary artery disease in the Australian hospital-based populationAtherosclerosis, 1999
- Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporinDigestive Diseases and Sciences, 1993