title: Supplemental antioxidants do not ameliorate colitis development in HLA-B27 transgenic rats despite extremely low glutathione levels in colonic mucosa.
abstract: BACKGROUND
  Oxidative stress is presumed to play an important role in inflammatory bowel disease (IBD). Accordingly, antioxidant supplementation might be protective. Dietary calcium inhibited colitis development in HLA-B27 transgenic rats, an animal model mimicking IBD. As antioxidants might act at mucosa level and calcium predominantly in the gut lumen, we hypothesize that the combination has additive protective effects on colitis development.
  
  
  METHODS
  HLA-B27 rats were fed a control diet or the same diet supplemented with the antioxidants glutathione, vitamin C, and vitamin E, or supplemented with both antioxidants and calcium. Oxidative stress in colonic mucosa, colonic inflammation, intestinal permeability, and diarrhea were quantified.
  
  
  RESULTS
  Intestinal permeability, diarrhea, myeloperoxidase, and interleukin-1β levels were significantly lower in rats fed both antioxidants and calcium compared to rats supplemented with antioxidants only. No beneficial effects were observed in rats fed the diet supplemented with antioxidants only. Strikingly, despite extremely low colonic mucosal glutathione levels in HLA-B27 rats, there was no oxidative stress-related damage. Subsequent analyses showed no defect in expression of glutathione synthesis genes. Additional experiments, comparing young and older HLA-B27 rats, showed that glutathione levels and also reactive oxygen species production decreased with progression of intestinal inflammation.
  
  
  CONCLUSIONS
  Antioxidant supplementation was ineffective in HLA-B27 rats despite low mucosal glutathione levels, because colitis development did not coincide with oxidative stress in this model. This indicates that the neutrophilic respiratory burst, and thus innate immune defense, is compromised in HLA-B27 rats. As supplementation with both calcium and antioxidants attenuated colitis development, we speculate that this protective effect is attributed to calcium only.
authors: TI Food and Nutrition, Wageningen, The Netherlands.
authors: Marloes A A
authors: MA
authors: Schepens
authors: Carolien
authors: C
authors: Vink
authors: Arjan J
authors: AJ
authors: Schonewille
authors: Hennie M J
authors: HM
authors: Roelofs
authors: Robert-Jan
authors: RJ
authors: Brummer
authors: Roelof
authors: R
authors: van der Meer
authors: Ingeborg M J
authors: IM
authors: Bovee-Oudenhoven
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D002136:Calcium, Dietary / Q000008:administration & dosage*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D015796:HLA-B27 Antigen / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D055647:Rats, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002136:Calcium, Dietary; D015796:HLA-B27 Antigen; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005978:Glutathione