Supplemental antioxidants do not ameliorate colitis development in HLA-B27 transgenic rats despite extremely low glutathione levels in colonic mucosa5

Schepens, Marloes A. A.; Vink, Carolien; Schonewille, Arjan J.; Roelofs, Hennie M.J.; Brummer, Robert Jan; Meer, Roelof van der; Bovee‐Oudenhoven, Ingeborg M. J.

doi:10.1002/ibd.21584

Cited by 15 publications

(10 citation statements)

References 39 publications

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“…These rats revealed several features that are also found in human IBD, such as reduced body weight, diarrhea, increased expression of proinflammatory genes such as COX-2, iNOS, TNFα, and IL1β in the colon mucosa, MPO activity, intestinal mucosal inflammation, and injury. In contrast, as demonstrated by other researchers [29], the development of colitis in HLA-B27 was not associated with an increase in oxidative DNA damage.…”

Section: Discussioncontrasting

confidence: 51%

Dietary Extra-Virgin Olive Oil Polyphenols Do Not Attenuate Colon Inflammation in Transgenic HLAB-27 Rats but Exert Hypocholesterolemic Effects through the Modulation of HMGCR and PPAR-α Gene Expression in the Liver

Bigagli¹,

Toti²,

Lodovici³

et al. 2018

Lifestyle Genomics

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Background: Human studies have demonstrated that olive oil phenolic compounds reduce inflammatory markers associated with chronic diseases. Objectives: To explore the anti-inflammatory effects of extra-virgin olive oil polyphenols in an experimental model of inflammatory bowel disease (IBD). Methods: HLA-B27 transgenic rats were fed an AIN-76 diet containing 10% corn oil (CO) or extra-virgin olive oil with high (EVOO) or low phenolic content (ROO) for 3 months. Wild-type rats (WT) were fed the CO diet. Results: CO-fed HLA-B27 animals developed intestinal inflammation characterized by diarrhea, increased myeloperoxidase activity, and mucosal injury. None of these parameters were influenced by EVOO. Gene expression profiling indicated that proinflammatory pathways were upregulated in the colon mucosa of CO-fed HLA-B27 rats compared to WT, and this was further confirmed by RT-PCR for the iNOS, TNFα, and IL1β genes. EVOO significantly reduced TNFα gene expression in the colon mucosa and decreased total cholesterol blood levels compared to CO HLA-B27 rats (89.43 ± 3.66 vs. 111.5 ± 8.10 mg/dL, p < 0.05). This latter effect with EVOO was associated with reduced HMGCR and increased PPAR-α hepatic gene expression, compared to ROO. Conclusion: These data indicate that olive oil polyphenols do not control colon inflammation in HLA-B27 transgenic rats but exert a positive effect on blood lipids by reducing total cholesterol levels. This preliminary result suggests the need to explore the efficacy of EVOO rich in polyphenols as a complementary strategy for managing hypercholesterolemia and to potentially limit statin-associated myotoxicity.

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Section: Discussioncontrasting

confidence: 51%

Dietary Extra-Virgin Olive Oil Polyphenols Do Not Attenuate Colon Inflammation in Transgenic HLAB-27 Rats but Exert Hypocholesterolemic Effects through the Modulation of HMGCR and PPAR-α Gene Expression in the Liver

Bigagli¹,

Toti²,

Lodovici³

et al. 2018

Lifestyle Genomics

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Section: Resultsmentioning

confidence: 99%

“…α-Tocopherol was utilized alone [47] and in combination with other nutrients [209] , [210] . Interestingly, the results had shown an absence of colonic antioxidant effect, when vitamin E was utilized with vitamin C and GSH [210] . Some meta-analyses have shown that antioxidant supplements do not result in the presumed health benefit, but paradoxically a high intake of antioxidants is associated with increased mortality [211] , [212] .…”

Section: Resultsmentioning

confidence: 99%

Antioxidant therapy for treatment of inflammatory bowel disease: Does it work?

et al. 2015

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Oxidative stress (OS) is considered as one of the etiologic factors involved in several signals and symptoms of inflammatory bowel diseases (IBD) that include diarrhea, toxic megacolon and abdominal pain. This systematic review discusses approaches, challenges and perspectives into the use of nontraditional antioxidant therapy on IBD, including natural and synthetic compounds in both human and animal models. One hundred and thirty four papers were identified, of which only four were evaluated in humans. Some of the challenges identified in this review can shed light on this fact: lack of standardization of OS biomarkers, absence of safety data and clinical trials for the chemicals and biological molecules, as well as the fact that most of the compounds were not repeatedly tested in several situations, including acute and chronic colitis. This review hopes to stimulate researchers to become more involved in this fruitful area, to warrant investigation of novel, alternative and efficacious antioxidant-based therapies.

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“…Decreased disease manifestations by N-acetylcysteine support this contention [129, 130]. However, the jury is still out on the causal role of mucosal GSH/GSSG disruption in IBD pathogenesis since antioxidant therapies with vitamin C, E, and GSH were without effect in the HLA-B27 transgenic rat model of IBD [131]. …”

Section: Intestinal Oxidative Stress and Gut Pathobiologymentioning

confidence: 99%

Intestinal redox biology and oxidative stress

Circu¹,

Aw²

2012

Seminars in Cell & Developmental Biology

272

192

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The intestinal epithelium sits at the interface between an organism and its luminal environment, and as such is prone to oxidative damage induced by luminal oxidants. Mucosal integrity is maintained by the luminal redox status of the glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) couples which also support luminal nutrient absorption, mucus fluidity, and a diverse microbiota. The epithelial layer is uniquely organized for rapid self-renewal that is achieved by the well-regulated processes of crypt stem cell proliferation and crypt-to-villus cell differentiation. The GSH/GSSG and Cys/CySS redox couples, known to modulate intestinal cell transition through proliferation, differentiation or apoptosis, could govern the regenerative potential of the mucosa. These two couples, together with that of the thioredoxin/thioredoxin disulfide (Trx/TrxSS) couple are the major intracellular redox systems, and it is proposed that they each function as distinctive redox control nodes or circuitry in the control of metabolic processes and networks of enzymatic reactions. Specificity of redox signaling is accomplished in part by subcellular compartmentation of the individual redox systems within the mitochondria, nucleus, endoplasmic reticulum, and cytosol wherein each defined redox environment is suited to the specific metabolic function within that compartment. Mucosal oxidative stress would result from the disruption of these unique redox control nodes, and the subsequent alteration in redox signaling can contribute to the development of degenerative pathologies of the intestine, such as inflammation and cancer.

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Supplemental antioxidants do not ameliorate colitis development in HLA-B27 transgenic rats despite extremely low glutathione levels in colonic mucosa5

Cited by 15 publications

References 39 publications

Dietary Extra-Virgin Olive Oil Polyphenols Do Not Attenuate Colon Inflammation in Transgenic HLAB-27 Rats but Exert Hypocholesterolemic Effects through the Modulation of HMGCR and PPAR-α Gene Expression in the Liver

Dietary Extra-Virgin Olive Oil Polyphenols Do Not Attenuate Colon Inflammation in Transgenic HLAB-27 Rats but Exert Hypocholesterolemic Effects through the Modulation of HMGCR and PPAR-α Gene Expression in the Liver

Antioxidant therapy for treatment of inflammatory bowel disease: Does it work?

Intestinal redox biology and oxidative stress

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