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

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          Abstract

          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.

          Graphical abstract

          Legend: 8-oxodG=8-oxo-2′-deoxyguanosine; AGE=advanced glycation end-products; COX2=cyclooxygenase 2; GR=glutathione reductase; GSH=reduced glutathione; iNOS=inducible nitric oxide synthase; GPx=glutathione peroxidase; GST=glutathione S-transferase; H 2O 2=hydrogen peroxide; LPO=lipoxygenase; MDA=malonaldheyde; NF-kB=nuclear factor Kappa-light-chain enhancer of activated B cells; Nrf2=nuclear erythroid 2 factor; NOX=NADPH oxidase; HO •=hydroxyl radical; O 2 •–=anion radical superoxide; NO •=nitric oxide; RONS=reactive oxygen and nitrogen species; SOD=superoxide dismutase; TBARS=thiobarbituric acid reactive substances; ˧ decrease; (–) inhibition; (+) stimulus.

          Highlights

          • •

            Major biomarkers used for evaluation of antioxidant therapy were MPO, TBARS/MDA and glutathione levels.

          • •

            Challenges were identified for the yet poor use of antioxidant therapy in IBD.

          • •

            This review stimulates the investigation of alternative and efficacious antioxidant therapies.

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          Most cited references304

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          Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee.

          Asher Kornbluth, David B Sachar (2010)
          Guidelines for clinical practice are aimed to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind placebo controlled studies are preferable, but compassionate-use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject regardless of specialty training or interests and are aimed to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the board of trustees. Each has been intensely reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision analysis. The recommendations of each guideline are therefore considered valid at the time of composition based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at a time established and indicated at publication to assure continued validity. The recommendations made are based on the level of evidence found. Grade A recommendations imply that there is consistent level 1 evidence (randomized controlled trials), grade B indicates that the evidence would be level 2 or 3, which are cohort studies or case-control studies. Grade C recommendations are based on level 4 studies, meaning case series or poor-quality cohort studies, and grade D recommendations are based on level 5 evidence, meaning expert opinion.
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            The chemistry and antioxidant properties of tocopherols and tocotrienols.

            A Kamal-Eldin, L Appelqvist (1996)
            This article is a review of the fundamental chemistry of the tocopherols and tocotrienols relevant to their antioxidant action. Despite the general agreement that alpha-tocopherol is the most efficient antioxidant and vitamin E homologue in vivo, there was always a considerable discrepancy in its "absolute" and "relative" antioxidant effectiveness in vitro, especially when compared to gamma-tocopherol. Many chemical, physical, biochemical, physicochemical, and other factors seem responsible for the observed discrepancy between the relative antioxidant potencies of the tocopherols in vivo and in vitro. This paper aims at highlighting some possible reasons for the observed differences between the tocopherols (alpha-, beta-, gamma-, and delta-) in relation to their interactions with the important chemical species involved in lipid peroxidation, specifically trace metal ions, singlet oxygen, nitrogen oxides, and antioxidant synergists. Although literature reports related to the chemistry of the tocotrienols are quite meager, they also were included in the discussion in virtue of their structural and functional resemblance to the tocopherols.
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              Melatonin as a natural ally against oxidative stress: a physicochemical examination.

              Annia Galano, Dun Tan, Russel Reiter (2011)
              Oxidative stress has been proven to be related to the onset of a large number of health disorders. This chemical stress is triggered by an excess of free radicals, which are generated in cells because of a wide variety of exogenous and endogenous processes. Therefore, finding strategies for efficiently detoxifying free radicals has become a subject of a great interest, from both an academic and practical points of view. Melatonin is a ubiquitous and versatile molecule that exhibits most of the desirable characteristics of a good antioxidant. The amount of data gathered so far regarding the protective action of melatonin against oxidative stress is overwhelming. However, rather little is known concerning the chemical mechanisms involved in this activity. This review summarizes the current progress in understanding the physicochemical insights related to the free radical-scavenging activity of melatonin. Thus far, there is a general agreement that electron transfer and hydrogen transfer are the main mechanisms involved in the reactions of melatonin with free radicals. However, the relative importance of other mechanisms is also analyzed. The chemical nature of the reacting free radical also has an influence on the relative importance of the different mechanisms of these reactions. Therefore, this point has also been discussed in detail in the current review. Based on the available data, it is concluded that melatonin efficiently protects against oxidative stress by a variety of mechanisms. Moreover, it is proposed that even though it has been referred to as the chemical expression of darkness, perhaps it could also be referred to as the chemical light of health. © 2011 John Wiley & Sons A/S.
              Article 0 comments Cited 305 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Fabiana Andréa Moura
                Kívia Queiroz de Andrade
                Juliana Célia Farias dos Santos
                Orlando Roberto Pimentel Araújo
                Marília Oliveira Fonseca Goulart
                Journal
                Journal ID (nlm-ta): Redox Biol
                Journal ID (iso-abbrev): Redox Biol
                Title: Redox Biology
                Publisher: Elsevier
                ISSN (Electronic): 2213-2317
                Publication date PMC-release: 23 October 2015
                Publication date Collection: December 2015
                Publication date (Electronic): 23 October 2015
                Volume: 6
                Pages: 617-639
                Affiliations
                [a ]Faculdade de Nutrição/Universidade Federal de Alagoas (FANUT/UFAL), Brazil
                [b ]Pós Graduação em Ciências da Saúde (PPGCS)/ Universidade Federal de Alagoas, Brazil
                [c ]Instituto de Química e Biotecnologia (IQB), Universidade Federal de Alagoas (UFAL), Brazil
                Author notes
                [* ]Correspondence to: Instituto de Química e Biotecnologia – Universidade Federal de Alagoas, Campus A. C. Simões, Avenida Lourival Melo Mota, s/n, Tabuleiro dos Martins, 57072-970 Maceió, AL, Brazil.Instituto de Química e Biotecnologia – Universidade Federal de AlagoasCampus A. C. Simões, Avenida Lourival Melo Mota, s/n, Tabuleiro dos MartinsMaceióAL57072-970Brazil mariliaofg@ 123456gmail.com
                Article
                Publisher ID: S2213-2317(15)00157-3
                DOI: 10.1016/j.redox.2015.10.006
                PMC ID: 4637335
                PubMed ID: 26520808
                SO-VID: 129204c9-167b-4c91-b55e-7fa589320177
                Copyright © © 2015 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 15 September 2015
                Date revision received : 18 October 2015
                Date accepted : 20 October 2015
                Categories
                Subject: Review Article

                Keywords: inflammatory bowel diseases,oxidative stress,nutraceuticals,antioxidant therapy,biomarkers,complementary and alternative medicine,ulcerative colitis,crohn's disease
                Data availability:
                Keywords: inflammatory bowel diseases, oxidative stress, nutraceuticals, antioxidant therapy, biomarkers, complementary and alternative medicine, ulcerative colitis, crohn's disease

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