Alterations in the glutathione metabolism could be implicated in the ischemia-induced small intestinal cell damage in horses.
Abstract: Colic could be accompanied by changes in the morphology and physiology of organs and tissues, such as the intestine. This process might be, at least in part, due to the accumulation of oxidative damage induced by reactive oxygen (ROS) and reactive nitrogen species (RNS), secondary to intestinal ischemia. Glutathione (GSH), being the major intracellular thiol, provides protection against oxidative injury. The aim of this study was to investigate whether ischemia-induced intestinal injury could be related with alterations in GSH metabolism. Results: Ischemia induced a significant increase in lipid hydroperoxides, nitric oxide and carbon monoxide, and a reduction in reduced glutathione, and adenosine triphosphate (ATP) content, as well as in methionine-adenosyl-transferase and methyl-transferase activities. Conclusions: Our results suggest that ischemia induces harmful effects on equine small intestine, probably due to an increase in oxidative damage and proinflammatory molecules. This effect could be mediated, at least in part, by impairment in glutathione metabolism.
Publication Date: 2009-03-18 PubMed ID: 19296836PubMed Central: PMC2664797DOI: 10.1186/1746-6148-5-10Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research article explores the association between changes in glutathione metabolism and potential damage to small intestinal cells in horses due to ischemia, a condition often linked to colic in such animals.
Research Purpose and Methodology
- The primary goal of the study was to examine whether damage to the intestinal tissue in horses resulting from ischemia is related to alterations in the metabolism of Glutathione (GSH), an important compound that protects against oxidative injury.
- Ischemia is a condition wherein the blood flow to an organ is reduced, causing a shortage of oxygen and glucose needed for cellular metabolism, which leads to cell damage and dysfunction.
- In this context, the researchers looked into a hypothetical scenario where ischemia-linked intestinal damage could be due to a build-up of oxidative harm caused by reactive oxygen (ROS) and reactive nitrogen species (RNS).
Investigation Outcomes
- The researchers observed a significant increase in lipid hydroperoxides, nitric oxide, and carbon monoxide following ischemia, which could be indicators of increased oxidative stress.
- Simultaneously, a reduction in reduced glutathione (an antioxidant form of GSH), adenosine triphosphate (ATP) content (required for energy in cells), and activities of enzymes like methionine-adenosyl-transferase and methyl-transferase were noted. Decreases in these components could contribute to cellular dysfunction.
Study Conclusion
- The study concluded that ischemia has harmful effects on the small intestine of horses, potentially due to an increase in oxidative damage and pro-inflammatory molecules.
- This harmful effect could be mediated in part by an impairment in glutathione metabolism. In other words, when glutathione metabolism gets impaired due to ischemia, it could lead to increased oxidative stress, causing further damage to the intestinal cells.
Cite This Article
APA
Marañón G, Manley W, Cayado P, García C, de la Muela MS, Vara E.
(2009).
Alterations in the glutathione metabolism could be implicated in the ischemia-induced small intestinal cell damage in horses.
BMC Vet Res, 5, 10.
https://doi.org/10.1186/1746-6148-5-10 Publication
Researcher Affiliations
- Horsepital SL, Villanueva del Pardillo, Madrid, Spain. gonzamara@yahoo.es
MeSH Terms
- Adenosine Triphosphate / metabolism
- Animals
- Carbon Monoxide / metabolism
- Glutathione / metabolism
- Horse Diseases / physiopathology
- Horses / physiology
- Intestine, Small / cytology
- Intestine, Small / enzymology
- Intestine, Small / metabolism
- Intestine, Small / physiopathology
- Ischemia / physiopathology
- Ischemia / veterinary
- Methionine Adenosyltransferase / metabolism
- Methyltransferases / metabolism
- Nitric Oxide / metabolism
References
This article includes 56 references
- Meyers K, Reed S, Keck M, Clem M, Bayly W. Circulating endotoxin-like substance(s) and altered hemostasis in horses with gastrointestinal disorders: an interim report.. Am J Vet Res 1982 Dec;43(12):2233-8.
- Welles EG, Prasse KW, Moore JN. Use of newly developed assays for protein C and plasminogen in horses with signs of colic.. Am J Vet Res 1991 Feb;52(2):345-51.
- Davis JL, Papich MG, Morton AJ, Gayle J, Blikslager AT, Campbell NB. Pharmacokinetics of etodolac in the horse following oral and intravenous administration.. J Vet Pharmacol Ther 2007 Feb;30(1):43-8.
- Tschetter JR, Blikslager AT, Little D, Howard RD, Woody SL, Beex LM, Crisman MV. Detection of differentially regulated genes in ischaemic equine intestinal mucosa.. Equine Vet J 2005 Jul;37(4):319-24.
- Moore RM. Clinical relevance of intestinal reperfusion injury in horses.. J Am Vet Med Assoc 1997 Dec 1;211(11):1362-6.
- Sastre J, Pallardó FV, Viña J. Mitochondrial oxidative stress plays a key role in aging and apoptosis.. IUBMB Life 2000 May;49(5):427-35.
- Reiter RJ, Tan DX, Cabrera J, D'Arpa D, Sainz RM, Mayo JC, Ramos S. The oxidant/antioxidant network: role of melatonin.. Biol Signals Recept 1999 Jan-Apr;8(1-2):56-63.
- Reiter RJ. Oxidative damage in the central nervous system: protection by melatonin.. Prog Neurobiol 1998 Oct;56(3):359-84.
- Ryter SW, Otterbein LE, Morse D, Choi AM. Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance.. Mol Cell Biochem 2002 May-Jun;234-235(1-2):249-63.
- Kaplowitz N, Aw TY, Ookhtens M. The regulation of hepatic glutathione.. Annu Rev Pharmacol Toxicol 1985;25:715-44.
- Dröge W. Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants.. Exp Gerontol 2002 Dec;37(12):1333-45.
- Meister A, Anderson ME. Glutathione.. Annu Rev Biochem 1983;52:711-60.
- Weinberg JM, Davis JA, Abarzua M, Rajan T. Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules.. J Clin Invest 1987 Nov;80(5):1446-54.
- Barclay LR. The cooperative antioxidant role of glutathione with a lipid-soluble and a water-soluble antioxidant during peroxidation of liposomes initiated in the aqueous phase and in the lipid phase.. J Biol Chem 1988 Nov 5;263(31):16138-42.
- Mårtensson J, Meister A. Mitochondrial damage in muscle occurs after marked depletion of glutathione and is prevented by giving glutathione monoester.. Proc Natl Acad Sci U S A 1989 Jan;86(2):471-5.
- Mårtensson J, Jain A, Meister A. Glutathione is required for intestinal function.. Proc Natl Acad Sci U S A 1990 Mar;87(5):1715-9.
- Mato JM, Alvarez L, Ortiz P, Pajares MA. S-adenosylmethionine synthesis: molecular mechanisms and clinical implications.. Pharmacol Ther 1997;73(3):265-80.
- Ko K, Yang H, Noureddin M, Iglesia-Ara A, Xia M, Wagner C, Luka Z, Mato JM, Lu SC. Changes in S-adenosylmethionine and GSH homeostasis during endotoxemia in mice.. Lab Invest 2008 Oct;88(10):1121-9.
- Semmler A, Smulders Y, Struys E, Smith D, Moskau S, Blom H, Linnebank M. Methionine metabolism in an animal model of sepsis.. Clin Chem Lab Med 2008;46(10):1398-402.
- White N. Examination and diagnosis of the acute abdomen. 102–142. Philadelphia: Lea & Febiger; 1990.
- OWENS CW, BELCHER RV. A COLORIMETRIC MICRO-METHOD FOR THE DETERMINATION OF GLUTATHIONE.. Biochem J 1965 Mar;94(3):705-11.
- Castillo C, Salazar V, Ariznavarreta C, Vara E, Tresguerres JA. Effect of recombinant human growth hormone on age-related hepatocyte changes in old male and female Wistar rats.. Endocrine 2004 Oct;25(1):33-9.
- Castillo C, Salazar V, Ariznavarreta C, Vara E, Tresguerres JA. Effect of growth hormone and estrogen administration on hepatocyte alterations in old ovariectomized female wistar rats.. Endocrine 2005 Feb;26(1):11-8.
- Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, Di Padova C. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study.. Gastroenterology 1990 Jul;99(1):211-5.
- Duce AM, Ortíz P, Cabrero C, Mato JM. S-adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis.. Hepatology 1988 Jan-Feb;8(1):65-8.
- Nosál'ová V, Navarová J, Mihalová D, Sotníková R. Mesenteric ischemia/reperfusion-induced intestinal and vascular damage: effect of stobadine.. Methods Find Exp Clin Pharmacol 2007 Jan-Feb;29(1):39-45.
- Tribble DL, Aw TY, Jones DP. The pathophysiological significance of lipid peroxidation in oxidative cell injury.. Hepatology 1987 Mar-Apr;7(2):377-86.
- Jackman BR, Moore JN, Barton MH, Morris DD. Comparison of the effects of ketoprofen and flunixin meglumine on the in vitro response of equine peripheral blood monocytes to bacterial endotoxin.. Can J Vet Res 1994 Apr;58(2):138-43.
- Boveris A, Alvarez S, Navarro A. The role of mitochondrial nitric oxide synthase in inflammation and septic shock.. Free Radic Biol Med 2002 Nov 1;33(9):1186-93.
- Szabó C. Multiple pathways of peroxynitrite cytotoxicity.. Toxicol Lett 2003 Apr 11;140-141:105-12.
- Chung HY, Kim HJ, Kim KW, Choi JS, Yu BP. Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction.. Microsc Res Tech 2002 Nov 15;59(4):264-72.
- Castillo C, Salazar V, Ariznavarreta C, Vara E, Tresguerres JA. Effect of recombinant human growth hormone on age-related hepatocyte changes in old male and female Wistar rats.. Endocrine 2004 Oct;25(1):33-9.
- Barocelli E, Ballabeni V, Ghizzardi P, Cattaruzza F, Bertoni S, Lagrasta CA, Impicciatore M. The selective inhibition of inducible nitric oxide synthase prevents intestinal ischemia-reperfusion injury in mice.. Nitric Oxide 2006 May;14(3):212-8.
- Fahey RC, Sundquist AR. Evolution of glutathione metabolism.. Adv Enzymol Relat Areas Mol Biol 1991;64:1-53.
- Ross D. Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection.. Pharmacol Ther 1988;37(2):231-49.
- Evans PJ, Whiteman M, Tredger JM, Halliwell B. Antioxidant properties of S-adenosyl-L-methionine: a proposed addition to organ storage fluids.. Free Radic Biol Med 1997;23(7):1002-8.
- De La Cruz JP, Villalobos MA, Cuerda MA, Guerrero A, González-Correa JA, Sánchez De La Cuesta F. Effects of S-adenosyl-L-methionine on lipid peroxidation and glutathione levels in rat brain slices exposed to reoxygenation after oxygen-glucose deprivation.. Neurosci Lett 2002 Jan 25;318(2):103-7.
- Arias-Díaz J, Vara E, García C, Villa N, Rodríguez JM, Ortiz P, Balibrea JL. S-adenosylmethionine protects hepatocytes against the effects of cytokines.. J Surg Res 1996 Apr;62(1):79-84.
- Avila MA, García-Trevijano ER, Martínez-Chantar ML, Latasa MU, Pérez-Mato I, Martínez-Cruz LA, del Pino MM, Corrales FJ, Mato JM. S-Adenosylmethionine revisited: its essential role in the regulation of liver function.. Alcohol 2002 Jul;27(3):163-7.
- Lieber CS. Role of S-adenosyl-L-methionine in the treatment of liver diseases.. J Hepatol 1999 Jun;30(6):1155-9.
- Lieber CS. S-Adenosyl-L-methionine and alcoholic liver disease in animal models: implications for early intervention in human beings.. Alcohol 2002 Jul;27(3):173-7.
- Mato JM, Cámara J, Fernández de Paz J, Caballería L, Coll S, Caballero A, García-Buey L, Beltrán J, Benita V, Caballería J, Solà R, Moreno-Otero R, Barrao F, Martín-Duce A, Correa JA, Parés A, Barrao E, García-Magaz I, Puerta JL, Moreno J, Boissard G, Ortiz P, Rodés J. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial.. J Hepatol 1999 Jun;30(6):1081-9.
- Frezza M, Centini G, Cammareri G, Le Grazie C, Di Padova C. S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial.. Hepatogastroenterology 1990 Dec;37 Suppl 2:122-5.
- Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, Di Padova C. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study.. Gastroenterology 1990 Jul;99(1):211-5.
- Muriel P, Suarez OR, Gonzalez P, Zuñiga L. Protective effect of S-adenosyl-l-methionine on liver damage induced by biliary obstruction in rats: a histological, ultrastructural and biochemical approach.. J Hepatol 1994 Jul;21(1):95-102.
- Belli DC, Fournier LA, Lepage G, Yousef I, Roy CC. S-adenosylmethionine prevents total parenteral nutrition-induced cholestasis in the rat.. J Hepatol 1994 Jul;21(1):18-23.
- Sánchez-Góngora E, Ruiz F, Mingorance J, An W, Corrales FJ, Mato JM. Interaction of liver methionine adenosyltransferase with hydroxyl radical.. FASEB J 1997 Oct;11(12):1013-9.
- Avila MA, Corrales FJ, Ruiz F, Sánchez-Góngora E, Mingorance J, Carretero MV, Mato IM. Specific interaction of methionine adenosyltransferase with free radicals.. Biofactors 1998;8(1-2):27-32.
- Ruiz F, Corrales FJ, Miqueo C, Mato JM. Nitric oxide inactivates rat hepatic methionine adenosyltransferase In vivo by S-nitrosylation.. Hepatology 1998 Oct;28(4):1051-7.
- Corrales F, Ochoa P, Rivas C, Martin-Lomas M, Mato JM, Pajares MA. Inhibition of glutathione synthesis in the liver leads to S-adenosyl-L-methionine synthetase reduction.. Hepatology 1991 Sep;14(3):528-33.
- Corrales FÁL, Pajares MA, Ortiz P, Mato JM. Impairment of methionine metabolism in liver disease. Drug Investigation 1992;4:8–13.
- Chawla RK, Jones DP. Abnormal metabolism of S-adenosyl-L-methionine in hypoxic rat liver. Similarities to its abnormal metabolism in alcoholic cirrhosis.. Biochim Biophys Acta 1994 Jan 5;1199(1):45-51.
- Barañano DE, Snyder SH. Neural roles for heme oxygenase: contrasts to nitric oxide synthase.. Proc Natl Acad Sci U S A 2001 Sep 25;98(20):10996-1002.
- Guo X, Shin VY, Cho CH. Modulation of heme oxygenase in tissue injury and its implication in protection against gastrointestinal diseases.. Life Sci 2001 Nov 9;69(25-26):3113-9.
- Henningsson R, Alm P, Lundquist I. Evaluation of islet heme oxygenase-CO and nitric oxide synthase-NO pathways during acute endotoxemia.. Am J Physiol Cell Physiol 2001 May;280(5):C1242-54.
- Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway.. Nat Med 2000 Apr;6(4):422-8.
Citations
This article has been cited 3 times.- Bardell D, Rocchigiani G, Ressel L, Milner P. Histological Evaluation of Resected Tissue as a Predictor of Survival in Horses with Strangulating Small Intestinal Disease.. Animals (Basel) 2023 Aug 26;13(17).
- Borunova SF, Tkachev N, Iolchiev B, Artyushina Z, Abramov P, Nikitina M, Silanteva A, Khusnetdinova N, Serezhenkov V. Estimation of Nitrite-Nitric Oxide Derivative-In Horses with Intestinal Colic by ESR Spectroscopy.. Vet Sci 2020 Nov 29;7(4).
- Morgaz J, Ventura S, Muñoz-Rascón P, Navarrete R, Pérez J, Granados MDM, Fernández-Sarmiento JA, Domínguez JM, Molina V, Gómez-Villamandos RJ, Zafra R. Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study.. BMC Vet Res 2020 Feb 12;16(1):54.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists