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Vo HVT, Kim N, Lee HJ. Vitamin Bs as Potent Anticancer Agents through MMP-2/9 Regulation. FRONT BIOSCI-LANDMRK 2025; 30:24072. [PMID: 39862072 DOI: 10.31083/fbl24072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 08/17/2024] [Accepted: 08/28/2024] [Indexed: 01/27/2025]
Abstract
In recent years, the role of coenzymes, particularly those from the vitamin B group in modulating the activity of metalloenzymes has garnered significant attention in cancer treatment strategies. Metalloenzymes play pivotal roles in various cellular processes, including DNA repair, cell signaling, and metabolism, making them promising targets for cancer therapy. This review explores the complex interplay between coenzymes, specifically vitamin Bs, and metalloenzymes in cancer pathogenesis and treatment. Vitamins are an indispensable part of daily life, essential for optimal health and well-being. Beyond their recognized roles as essential nutrients, vitamins have increasingly garnered attention for their multifaceted functions within the machinery of cellular processes. In particular, vitamin Bs have emerged as a pivotal regulator within this intricate network, exerting profound effects on the functionality of metalloenzymes. Their ability to modulate metalloenzymes involved in crucial cellular pathways implicated in cancer progression presents a compelling avenue for therapeutic intervention. Key findings indicate that vitamin Bs can influence the activity and expression of metalloenzymes, thereby affecting processes such as DNA repair and cell signaling, which are critical in cancer development and progression. Understanding the mechanisms by which these coenzymes regulate metalloenzymes holds great promise for developing novel anticancer strategies. This review summarizes current knowledge on the interactions between vitamin Bs and metalloenzymes, highlighting their potential as anticancer agents and paving the way for innovative, cell-targeted cancer treatments.
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Affiliation(s)
- Ha Vy Thi Vo
- Department of Chemistry Education, Kongju National University, 32588 Gongju, Chungcheongnam-do, Republic of Korea
| | - Namdoo Kim
- Department of Chemistry, Kongju National University, 32588 Gongju, Chungcheongnam-do, Republic of Korea
| | - Hyuck Jin Lee
- Department of Chemistry Education, Kongju National University, 32588 Gongju, Chungcheongnam-do, Republic of Korea
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Tang J, Wu Y, Zhang B, Liang S, Guo Z, Hu J, Zhou Z, Xie M, Hou S. Integrated liver proteomics and metabolomics identify metabolic pathways affected by pantothenic acid deficiency in Pekin ducks. ANIMAL NUTRITION 2022; 11:1-14. [PMID: 35950191 PMCID: PMC9356036 DOI: 10.1016/j.aninu.2022.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 02/07/2022] [Accepted: 03/18/2022] [Indexed: 10/25/2022]
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Pravda J. Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide. World J Gastroenterol 2022; 28:4263-4298. [PMID: 36159014 PMCID: PMC9453768 DOI: 10.3748/wjg.v28.i31.4263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 04/19/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
In this comprehensive evidence-based analysis of ulcerative colitis (UC), a causal role is identified for colonic epithelial hydrogen peroxide (H2O2) in both the pathogenesis and relapse of this debilitating inflammatory bowel disease. Studies have shown that H2O2 production is significantly increased in the non-inflamed colonic epithelium of individuals with UC. H2O2 is a powerful neutrophilic chemotactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular “trail” that attracts adjacent intravascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC. A novel therapy aimed at removing the inappropriate H2O2 mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one (biopsy-proven) histologic remission lasting 14 years to date. The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H2O2 mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease. Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects. It is the aim of this paper to present experimental and clinical evidence that identifies H2O2 produced by the colonic epithelium as the causal agent in the pathogenesis of UC. A detailed explanation of a novel therapeutic intervention to normalize colonic H2O2, its rationale, components, and formulation is also provided.
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Affiliation(s)
- Jay Pravda
- Disease Pathogenesis, Inflammatory Disease Research Centre, Palm Beach Gardens, FL 33410, United States
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Hrubša M, Siatka T, Nejmanová I, Vopršalová M, Kujovská Krčmová L, Matoušová K, Javorská L, Macáková K, Mercolini L, Remião F, Máťuš M, Mladěnka P, on behalf of the OEMONOM. Biological Properties of Vitamins of the B-Complex, Part 1: Vitamins B 1, B 2, B 3, and B 5. Nutrients 2022; 14:484. [PMID: 35276844 PMCID: PMC8839250 DOI: 10.3390/nu14030484] [Citation(s) in RCA: 76] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/16/2022] [Accepted: 01/17/2022] [Indexed: 02/06/2023] Open
Abstract
This review summarizes the current knowledge on essential vitamins B1, B2, B3, and B5. These B-complex vitamins must be taken from diet, with the exception of vitamin B3, that can also be synthetized from amino acid tryptophan. All of these vitamins are water soluble, which determines their main properties, namely: they are partly lost when food is washed or boiled since they migrate to the water; the requirement of membrane transporters for their permeation into the cells; and their safety since any excess is rapidly eliminated via the kidney. The therapeutic use of B-complex vitamins is mostly limited to hypovitaminoses or similar conditions, but, as they are generally very safe, they have also been examined in other pathological conditions. Nicotinic acid, a form of vitamin B3, is the only exception because it is a known hypolipidemic agent in gram doses. The article also sums up: (i) the current methods for detection of the vitamins of the B-complex in biological fluids; (ii) the food and other sources of these vitamins including the effect of common processing and storage methods on their content; and (iii) their physiological function.
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Affiliation(s)
- Marcel Hrubša
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Kralove, Czech Republic; (M.H.); (M.V.); (P.M.)
| | - Tomáš Siatka
- Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Kralove, Czech Republic; (T.S.); (K.M.)
| | - Iveta Nejmanová
- Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Kralove, Czech Republic;
| | - Marie Vopršalová
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Kralove, Czech Republic; (M.H.); (M.V.); (P.M.)
| | - Lenka Kujovská Krčmová
- Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Kralove, Czech Republic;
- Department of Clinical Biochemistry and Diagnostics, University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Kralove, Czech Republic; (K.M.); (L.J.)
| | - Kateřina Matoušová
- Department of Clinical Biochemistry and Diagnostics, University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Kralove, Czech Republic; (K.M.); (L.J.)
| | - Lenka Javorská
- Department of Clinical Biochemistry and Diagnostics, University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Kralove, Czech Republic; (K.M.); (L.J.)
| | - Kateřina Macáková
- Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Kralove, Czech Republic; (T.S.); (K.M.)
| | - Laura Mercolini
- Research Group of Pharmaco-Toxicological Analysis (PTA Lab), Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy;
| | - Fernando Remião
- UCIBIO—Applied Molecular Biosciences Unit, REQUINTE, Toxicology Laboratory, Biological Sciences Department Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal;
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
| | - Marek Máťuš
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Odbojárov 10, 83232 Bratislava, Slovak Republic
| | - Přemysl Mladěnka
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Kralove, Czech Republic; (M.H.); (M.V.); (P.M.)
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Tang J, Feng Y, Zhang B, Wu Y, Guo Z, Liang S, Zhou Z, Xie M, Hou S. Severe pantothenic acid deficiency induces alterations in the intestinal mucosal proteome of starter Pekin ducks. BMC Genomics 2021; 22:491. [PMID: 34193047 PMCID: PMC8246668 DOI: 10.1186/s12864-021-07820-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 06/18/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Pantothenic acid deficiency (PAD) results in growth depression and intestinal hypofunction of animals. However, the underlying molecular mechanisms remain to be elucidated. Mucosal proteome might reflect dietary influences on physiological processes. RESULTS A total of 128 white Pekin ducks of one-day-old were randomly assigned to two groups, fed either a PAD or a pantothenic acid adequate (control, CON) diet. After a 16-day feeding period, two ducks from each replicate were sampled to measure plasma parameters, intestinal morphology, and mucosal proteome. Compared to the CON group, high mortality, growth retardation, fasting hypoglycemia, reduced plasma insulin, and oxidative stress were observed in the PAD group. Furthermore, PAD induced morphological alterations of the small intestine indicated by reduced villus height and villus surface area of duodenum, jejunum, and ileum. The duodenum mucosal proteome of ducks showed that 198 proteins were up-regulated and 223 proteins were down-regulated (> 1.5-fold change) in the PAD group compared to those in the CON group. Selected proteins were confirmed by Western blotting. Pathway analysis of these proteins exhibited the suppression of glycolysis and gluconeogenesis, fatty acid beta oxidation, tricarboxylic acid cycle, oxidative phosphorylation, oxidative stress, and intestinal absorption in the PAD group, indicating impaired energy generation and abnormal intestinal absorption. We also show that nine out of eleven proteins involved in regulation of actin cytoskeleton were up-regulated by PAD, probably indicates reduced intestinal integrity. CONCLUSION PAD leads to growth depression and intestinal hypofunction of ducks, which are associated with impaired energy generation, abnormal intestinal absorption, and regulation of actin cytoskeleton processes. These findings provide insights into the mechanisms of intestinal hypofunction induced by PAD.
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Affiliation(s)
- Jing Tang
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Yulong Feng
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.,Guizhou Animal Husbandry and Veterinary Research Institute, Guizhou Academy of Agricultural Sciences, Guiyang, 550000, Guizhou, China
| | - Bo Zhang
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Yongbao Wu
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Zhanbao Guo
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Suyun Liang
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Zhengkui Zhou
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Ming Xie
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Shuisheng Hou
- State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
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Roediger WEW. Causation of human ulcerative colitis: A lead from an animal model that mirrors human disease. JGH Open 2019; 3:277-280. [PMID: 31406919 PMCID: PMC6684511 DOI: 10.1002/jgh3.12212] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 04/23/2019] [Accepted: 05/04/2019] [Indexed: 02/06/2023]
Abstract
Most models of experimental colitis do not replicate human ulcerative colitis and do not help in defining the causation of human ulcerative colitis. Inducing pantothenic acid deficiency in pigs produces an ideal model in terms of extent, histology, and chronicity of human ulcerative colitis. Comparing metabolic changes in human ulcerative colitis with metabolic changes in experimental colitis in pigs provided a guide for the search of initiating factors of human ulcerative colitis. Observations showed that bacterial nitric oxide with bacterial hydrogen sulphide reproduced the metabolic changes of human ulcerative colitis. Decreasing colon-produced nitric oxide and hydrogen sulphide by bacteria through diet and medication resulted in pronounced therapeutic improvement, both clinically and histologically, of human ulcerative colitis.
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Affiliation(s)
- William E W Roediger
- Department of Surgery and GastroenterologyUniversity of Adelaide at The Queen Elizabeth HospitalAdelaideAustralia
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Qian Y, Li XF, Zhang DD, Cai DS, Tian HY, Liu WB. Effects of dietary pantothenic acid on growth, intestinal function, anti-oxidative status and fatty acids synthesis of juvenile blunt snout bream Megalobrama amblycephala. PLoS One 2015; 10:e0119518. [PMID: 25781913 PMCID: PMC4362765 DOI: 10.1371/journal.pone.0119518] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2014] [Accepted: 01/28/2015] [Indexed: 11/30/2022] Open
Abstract
Four groups of juvenile Megalobrama amblycephala were fed three times daily with six semi-purified diets containing 3.39 (PA unsupplied diet), 10.54, 19.28, 31.04, 48.38 and 59.72 mg kg-1 calcium D-pantothenate. The results showed that survival rate, final weight, specific growth rate, protein efficiency ratio and nitrogen retention efficiency all increased significantly (P<0.01) as dietary PA levels increased from 3.39 to 19.28 mg kg-1, whereas the opposite was true for feed conversion ratio. Whole-body crude protein increased as dietary PA levels increased, while the opposite pattern was found for the crude lipid content. Intestinal α-amylase, lipase, protease, Na+-K+-ATPase, alkaline phosphatase and gamma-glutamyl transferase activities were all elevated in fish fed PA-supplemented diets. Hepatic catalase activities improved with increases in dietary PA, while the opposite was true for malondialdehyde contents. The liver PA concentration and coenzyme A content rose significantly (P<0.01), up to 31.04 mg kg-1, with increasing dietary PA levels and then plateaued. The percentage of hepatic saturated fatty acids increased significantly (P<0.01) as dietary PA levels increased, while the percentages of monounsaturated fatty acids and polyunsaturated fatty acid (PUFA) decreased as dietary PA increased. Fish fed diets containing 19.28 and 31.04 mg kg-1 PA exhibited higher (P<0.01) docosahexaenoic acid and PUFA percentages in muscle than those fed with other diets. The expression of the gene encoding pantothenate kinase was significantly up-regulated (P<0.01) in fish fed PA-supplemented diets. Hepatic Acetyl-CoA carboxylase α, fatty acid synthetase, stearoyl regulatory element-binding protein 1 and X receptor α genes all increased significantly (P<0.01) as dietary PA levels increased from 3.39 to 31.04 mg kg-1. Based on broken-line regression analyses of weight gain, liver CoA concentrations and PA contents against dietary PA levels, the optimal dietary PA requirements of juvenile blunt snout bream were estimated to be 24.08 mg kg-1.
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Affiliation(s)
- Yu Qian
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu Province, People's Republic of China
| | - Xiang-Fei Li
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu Province, People's Republic of China
| | - Ding-Dong Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu Province, People's Republic of China
| | - Dong-Sen Cai
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu Province, People's Republic of China
| | - Hong-Yan Tian
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu Province, People's Republic of China
| | - Wen-Bin Liu
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu Province, People's Republic of China
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Roediger WEW. Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis. Aliment Pharmacol Ther 2008; 27:531-41. [PMID: 18194497 DOI: 10.1111/j.1365-2036.2008.03612.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Factors initiating human ulcerative colitis (UC) are unknown. Dysbiosis of bacteria has been hypothesized to initiate UC but, to date, neither the nature of the dysbiosis nor mucosal breakdown has been explained. AIM To assess whether a dysbiosis of anaerobic nitrate respiration could explain the microscopic, biochemical and functional changes observed in colonocytes of UC. METHODS Published results in the gastroenterological, biochemical and microbiological literature were reviewed concerning colonocytes, nitrate respiration and nitric oxide in the colon in health and UC. A best-fit explanation of results was made regarding the pathogenesis and new treatments of UC. RESULTS Anaerobic nitrate respiration yields nitrite, nitric oxide (NO) and nitrous oxide. Colonic bacteria produce NO and UC in remission has a higher lumenal NO level than control cases. NO with sulphide, but not NO alone, impairs beta-oxidation, lipid and protein synthesis explaining the membrane, tight junctional and ion channel changes observed in colonocytes of UC. The observations complement therapeutic mechanisms of those probiotics, prebiotics and antibiotics useful in treating UC. CONCLUSIONS The prolonged production of bacterial NO with sulphide can explain the initiation and barrier breakdown, which is central to the pathogenesis of UC. Therapies to alter bacterial nitrate respiration and NO production need to evolve. The production of NO by colonic bacteria and that of the mucosa need to be separated to pinpoint the sequential nature of NO damage in UC.
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Affiliation(s)
- W E W Roediger
- University of Adelaide Department of Surgery, The Queen Elizabeth Hospital, Woodville, SA, Australia.
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Roediger WE, Babidge WJ. Nitric oxide effect on colonocyte metabolism: co-action of sulfides and peroxide. Mol Cell Biochem 2000; 206:159-67. [PMID: 10839206 DOI: 10.1023/a:1007034417320] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Luminal levels of nitric oxide/nitrite are high in colitis. Whether nitric oxide is injurious or protective to human colonocytes is unknown and the role of nitric oxide in the genesis of colitis unclear. The aims were to establish whether nitric oxide was injurious to oxidation of substrates (n-butyrate and D-glucose) in isolated human and rat colonocytes both alone and in the presence of hydrogen sulfide and hydrogen peroxide, agents implicated in cell damage of colitis. Nitric oxide generation from S-nitrosoglutathione was measured by nitrite appearance. Colonocytes were isolated and incubated with [1-14C] butyrate or [6-14C] glucose and 2.6 microM nitric oxide, 1.5 mM sodium hydrogen sulfide or 2.5 mM hydrogen peroxide. Acyl-CoA esters were measured by high performance liquid chromatography, 14CO2 radiochemically and lactate/ketones by enzymic methods. Results indicate that nitric oxide very significantly (p < .001) reduced acyl-CoA formation but did not impair 14CO2 generation. Peroxide and sulfide with nitric oxide resulted in significant reduction (p < 0.01) of substrate oxidation to CO2. Sulfide significantly stimulated release of nitric oxide from S-nitrosoglutathione. The principal conclusion is that nitric oxide diminishes CoA metabolism in colonocytes. CoA depletion has been observed in chronic human colitis for which a biochemical explanation has been lacking. For acute injurious action in human colonocytes nitric oxide requires co-action of peroxide and sulfide to impair oxidation of substrates in cells. From current observations treatment of colitis should aim to reduce simultaneously nitric oxide, peroxide and sulfide generation in the colon.
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Affiliation(s)
- W E Roediger
- Department of Surgery, University of Adelaide at The Queen Elizabeth Hospital, Australia
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Loftus EV, Tremaine WJ, Nelson RA, Shoemaker JD, Sandborn WJ, Phillips SF, Hasan Y. Dexpanthenol enemas in ulcerative colitis: a pilot study. Mayo Clin Proc 1997; 72:616-20. [PMID: 9212762 DOI: 10.1016/s0025-6196(11)63566-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To test the hypothesis that topical administration of pantothenic acid, a precursor of coenzyme A, might result in increased tissue levels of coenzyme A, improvement of fatty acid oxidation, and amelioration of ulcerative colitis. MATERIAL AND METHODS In an open-label pilot study, three patients with active left-sided ulcerative colitis received nightly enemas that contained 1,000 mg of dexpanthenol for 4 weeks. Before and after the study, patients submitted stool specimens for short-chain fatty acid analysis and urine collections for measurement of pantothenic acid and dicarboxylic acids; they also underwent flexible sigmoidoscopy for procurement of biopsy specimens for histologic examination and measurement of colonic coenzyme A activity. A clinical disease activity index and histologic disease activity index were used to assess response. RESULTS Despite increases in urinary pantothenic acid, no significant changes were found in colonic tissue coenzyme A concentrations, fecal short-chain fatty acid concentrations, or urinary dicarboxylic acid concentrations. Moreover, no significant changes in clinical or histologic disease activity were noted. Although stool frequency and rectal bleeding remained unchanged, all patients noted increased abdominal cramping, and one patient had an increased extent of disease. CONCLUSION Topically administered dexpanthenol seems to be absorbed, but at the dose used in this study, it did not influence concentrations of colonic coenzyme A activity, fecal short-chain fatty acids, or clinical response in patients with active left-sided ulcerative colitis.
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Affiliation(s)
- E V Loftus
- Division of Gastroenterology and Internal Medicine, Mayo Clinic Rochester, MN 55905, USA
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Burke A, Lichtenstein GR, Rombeau JL. Nutrition and ulcerative colitis. BAILLIERE'S CLINICAL GASTROENTEROLOGY 1997; 11:153-74. [PMID: 9192066 DOI: 10.1016/s0950-3528(97)90059-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The role of diet in the aetiology and pathogenesis of ulcerative colitis (UC) remains uncertain. Impaired utilization by colonocytes of butyrate, a product of bacterial fermentation of dietary carbohydrates escaping digestion, may be important. Sulphur-fermenting bacteria may be involved in this impaired utilization. Oxidative stress probably mediates tissue injury but is probably not of causative importance. Patients with UC are prone to malnutrition and its detrimental effects. However, there is no role for total parenteral nutrition and bowel rest as primary therapy for UC. The maintenance of adequate nutrition is very important, particularly in the peri-operative patient. In the absence of massive bleeding, perforation, toxic megacolon or obstruction, enteral rather than parenteral nutrition should be the mode of choice. Nutrients may be beneficial as adjuvant therapy. Butyrate enemas have improved patients with otherwise recalcitrant distal colitis in small studies. Non-cellulose fibre supplements are of benefit in rats with experimental colitis. Eicosapentaenoic acid in fish oil has a steroid-sparing effect which, although modest, is important, particularly in terms of reducing the risk of osteoporosis, but it seems to have no role in the patient with inactive disease. gamma-Linolenic acid and anti-oxidants also are showing promise. Nutrients may also modify the increased risk of colorectal carcinoma. Oxidative stress can damage tissue DNA but there are no data published at present on possible protection from oral anti-oxidants. Butyrate protects against experimental carcinogenesis in rats with experimental colitis. Folate supplementation is weakly associated with decreased incidence of cancer in UC patients when assessed retrospectively. Vigilance should be maintained for increased micronutrient requirements and supplements given as appropriate. Calcium and low-dose vitamin D should be given to patients on long-term steroids and folate to those on sulphasalazine.
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Affiliation(s)
- A Burke
- Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104, USA
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Affiliation(s)
- G Latella
- Dipartimento di Medicina Interna e Sanità Pubblica, Università degli studi Dell'Aquila, Italy
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Abstract
In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
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Affiliation(s)
- A G Tahiliani
- Geisinger Clinic, Weis Center for Research, Danville, Pennsylvania 17822
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14
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Roediger WE, Nance S. Selective reduction of fatty acid oxidation in colonocytes: correlation with ulcerative colitis. Lipids 1990; 25:646-52. [PMID: 2127822 DOI: 10.1007/bf02536016] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Attempts were made to define which fatty acid (2:0 to 18:1) was optimally oxidized by isolated colonocytes (colonic epithelial cells) and to select inhibitors of fatty acid oxidation which would be analogous in their action to the inhibition of fatty acid oxidation observed in colonocytes involved with ulcerative colitis. Isolated colonic epithelial cells of Sprague-Dawley rats were used with 2-mercaptoacetate, dichloroacetate, 3-mercaptopropionate, 4-mercaptobutyrate, 4-sulfatebutyrate, 2-bromobutyrate, sulfite ions and nitrite ions. n-Butyrate (4:0) was maximally oxidized to CO2 and ketone bodies (mean value 5.46 mumols/min/g dry wt). Oxidation of butyrate to CO2 was diminished by 2-bromobutyrate, sulfite ions and all mercapto fatty acids. Both fatty acid oxidation and glucose oxidation were significantly inhibited by 2-bromobutyrate, while mercapto fatty acids and sulfite inhibited fatty acid oxidation (p less than 0.01) without significantly changing glucose oxidation. Observation with 2-mercaptoacetate and sulfite correlate with early changes of fatty acid oxidation observed in cases of ulcerative colitis, and warrant further study with isolated colonocytes of man.
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Affiliation(s)
- W E Roediger
- Department of Surgery, Queen Elizabeth Hospital, Australia
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15
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Abstract
Impaired metabolism of short-chain fatty acids, as well as a modified fecal ionogram, have been reported in ulcerative colitis. Fecal water samples from 62 patients with ulcerative colitis were analyzed in the present investigation to evaluate changes in SCFAs and lactic acid in relation to activity and severity of disease. Short-chain fatty acid levels were high in quiescent and mild disease (162.6 +/- 63.6 and 147.8 +/- 63.2 mM/L, respectively), but significantly decreased in the severe form (64.7 +/- 46.9 mM/L). Lactate showed a progressive increase from mild colitis (3.0 +/- 1.8 mM/L) to severe colitis (21.4 +/- 18.6 mM/L). It thus appears that mild colitis displayed a fecal pattern characterized by normal pH and bicarbonate, slightly impaired electrolyte handling, high short-chain fatty acid values, and only moderately increased lactate. Severe colitis, on the other hand, was characterized by low fecal pH, bicarbonate, and potassium, high sodium and chloride, low short-chain fatty acid levels, and very high lactate levels. A critical lowering of intraluminal pH, which shifts bacterial metabolism from short-chain fatty acid to lactate production, may be responsible for the intraluminal pooling of lactate.
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Affiliation(s)
- P Vernia
- Department of Gastroenterology, Università La Sapienza, Rome, Italy
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16
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Smith CM, Narrow CM, Kendrick ZV, Steffen C. The effect of pantothenate deficiency in mice on their metabolic response to fast and exercise. Metabolism 1987; 36:115-21. [PMID: 3807784 DOI: 10.1016/0026-0495(87)90003-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The changes in fuel metabolism during fast and exercise were compared to the tissue total CoA levels in mice maintained on pantothenate-deficient and pantothenate-supplemented (control) diets. In nonexercised mice maintained on a pantothenate-deficient diet for 65 to 105 days, the total CoA levels of many tissues were significantly lower than in controls (liver 18%, kidney 23%, spleen 21%, heart 38%, and leg skeletal muscle 66%). However, no differences in total CoA levels in brain or epididymal fat pads were observed. During a 48-hour fast, the total CoA levels increased in the heart and liver of both pantothenate-deficient and control mice (heart 32 and 19%, respectively; liver 39 and 45%, respectively), but the level of total CoA remained lower in the deficient mice. Liver glycogen levels were 17% lower in deficient mice than in controls and liver ketone bodies were 17% higher in pantothenate deficient mice than in controls. Separate groups of mice on deficient and supplemented diets were trained to run to exhaustion. Compared to trained mice on pantothenate-supplemented diets, the trained pantothenate-deficient mice had lower running times until exhaustion, lower body weights, lower liver and muscle glycogen content (even after rest), and elevated liver ketone bodies both during rest and after running. In summary, the pantothenate-deficient mice were unable to maintain normal glycogen stores, but had a normal ketogenic response to fast and exercise in spite of the lower levels of liver total CoA.
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17
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18
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Low AG, Low AG, Low AG. Nutrient absorption in pigs. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 1980; 31:1087-1130. [PMID: 7017272 DOI: 10.1002/jsfa.2740311102] [Citation(s) in RCA: 72] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
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19
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Abstract
Suspensions of colonocytes (isolated colonic epithelial cells) were prepared from mucosa of the descending colon from 6 patients with quiescent ulcerative colitis (UC), 4 with acute UC, and 7 control subjects. In each group metabolic performance was investigated by assessing utilisation of n-butyrate, the main respiratory fuel of the colonic mucosa, as well as utilisation of glucose and glutamine. In both acute and quiescent UC oxidation of butyrate to CO2 and ketones was significantly lower than in the control tissues, and the decrease correlated with the state of the disease. Enhanced glucose and glutamine oxidation compensated for decreased butyrate oxidation in UC, indicating that colonocytes in colitis were not metabolically degenerate cells. Failure of butyrate oxidation reflects a variable yet definite metabolic defect in the mucosa in UC. Diminished oxidation of butyrate can explain the characteristic distribution of colitis along the colon, especially the frequency of UC in the distal colon. It is suggested that failure of fatty-acid (n-butyrate) oxidation in UC is an expression of an energy-deficiency disease of the colonic mucosa.
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20
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Herman RH. The Interaction between the Gastrointestinal Tract and Nutrient Intake. Nutrition 1979. [DOI: 10.1007/978-1-4615-7213-8_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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21
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Partridge IG. Studies on digestion and absorption in the intestines of growing pigs. 3. Net movements of mineral nutrients in the digestive tract. Br J Nutr 1978; 39:527-37. [PMID: 638122 DOI: 10.1079/bjn19780068] [Citation(s) in RCA: 55] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
1. Pigs growing from 20 to 60 kg live weight were given diets based on barley, weatings and fish meal, or starch, sucrose and groundnut meal or starch, sucrose and casein. Seventeen pigs were fitted with single re-entrant cannulas in the duodenum (posterior to entry of bile and pancreatic ducts), jejunum or terminal ileum and twenty-four non-cannulated pigs were used in a conventional digestibility trial. 2. The amounts of calcium, phosphorus, magnesium, sodium and potassium passing through the re-entrant cannulas and amounts excreted in the faeces were measured. These values were used to calculate the direction and extent of net movements of the five elements through the walls of the four parts of the digestive tract anterior to the collection sites. 3. The small intestine was the principal site of Ca and P absorption but there were differences between the diets in the relative importance of the regions anterior and posterior to the mid-jejunum. 4. Secretion of small amounts of Mg occurred in the anterior small intestine; the ileum and large intestine were the principal sites of net absorption. 5. There was a large net secretion of Na anterior to the duodenal cannulas and further secretion into the anterior small intestine with each diet. There were marked differences between diets in the amounts secreted but the ileal Na concentration was the same in each instance. Absorption occurred in the ileum and large intestine. 6. Secretion of small amounts of K was evident anterior to the duodenal cannulas and net absorption occurred in both parts of the small intestine with each diet.
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22
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Ramakrishnan CV, Subramoniam A. Effect of prenatal and neonatal pantothenic acid deficiency on rat intestinal phosphatases. Cell Mol Life Sci 1978; 34:435-437. [PMID: 639935 DOI: 10.1007/bf01935910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Alkaline phosphatase activity was increased in the distal part of the small intestine of pantothenic acid deficient neonatal rats, while acid phosphatase activity was slightly increased and protein concentration was decreased throughout the small intestine. The growth and maturation of the distal part of the small intestine were retarded more severely than in the proximal part.
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