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AGE

, Volume 22, Issue 4, pp 149–158 | Cite as

A glyconutritional mixture (Ambrotose®) provides some amelioration to mice with coxsackievirus-induced pancreatitis

  • C. Gauntt
  • D. Busbee
  • H. J. Wood
  • S. Reyna
  • R. Barhoumi
  • R. Burghardt
  • W. McAnalley
  • H. R. McDaniel
Article
  • 61 Downloads

Abstract

Challenge of adolescent male CD-1 mice with a coxsackievirus B3 (CVB3) strain (CVB3m) induces mild to severe destruction of pancreatic acinar cells, but causes no deaths and does not induce hyperglycemia. A weekly parenteral (intraperitoneal) administration of a glyconutritional mixture (Ambrotose® to virus-challenged mice was assessed to determine if there were any benefits to recovery over an eight month period. Virus-challenged mice showed a significant weight loss over the initial five weeks of the experiment, but injection of Ambrotose® to similar virus-challenged mice restored the total body weight to levels found in normal mice. Normal mice given Ambrotose® exhibited a small weight gain. Mice given Ambrotose® showed reduced severity of pancreatitis, as evidenced by significant reductions in percentages of pancreatic acinar cells destroyed and proportion of sections of pancreata with destroyed acinar cells, compared to virus control-mice not injected with Ambrotose®. Statistical analyses of the extent of acinar cell pathology in all virus-challenged mice showed that Ambrotose® contributed significantly to recovery of the acinar cell population in virus-inoculated mice. Anti-viral antibody titers were not affected by Ambrotose® injections. One potential mechanism to explain the benefits derived from Ambrotose® injections came from studies of antioxidant levels of glutathione in splenic macrophages/monocytes. Whereas CVB3 challenge of mice reduced glutathione levels in the latter cells, Ambrotose® injections to virus-challenged mice restored glutathione levels to those found in normal mice. In summary, most but not all mice derived benefits from Ambrotose® injections, i.e. a reduction in pathology in the pancreas and restored levels of the antioxidant glutathione in macrophages/monocytes. Higher doses of Ambrotose® could provide greater benefits for more mice, a study for the future.

Keywords

Pancreatitis Hyperglycemia Acinar Cell Normal Mouse Reduce Glutathione 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Atkinson, MA, Bowman, MA, Campbell, L, Darrow, BL, Kaufman, DL, and Maclaren, NK: Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J. Clin. Invest., 94:2125–2129, 1994.PubMedGoogle Scholar
  2. Barhoumi, R, Bailey, RH, and Burghardt, RC: Kinetic analysis of glutathione in anchored cells with monochlorobimane. Cytometry, 19:226–234, 1995.PubMedCrossRefGoogle Scholar
  3. Barhoumi, R, Burghardt, RC, Busbee, DL, and McDaniel, HR: Enhancement of glutathione levels and protection from chemically initiated glutathione depletion in rat liver cells by glyconutritionals. Proc. Fisher Inst. Med. Res., 1:12–16, 1997.Google Scholar
  4. Bilchik, AJ, Leach, SD, Zucker, KA, and Modlin, IM: Experimental models of acute pancreatitis. J. Surg. Res., 48:639–647, 1990.PubMedCrossRefGoogle Scholar
  5. Bockman, DE: Toward understanding pancreatic disease: from architecture to cell signaling. Pancreas, 11: 324–329, 1995.PubMedCrossRefGoogle Scholar
  6. Bockman, DE: Morphology of the exocrine pancreas related to pancreatitis. Microsc. Res. Tech., 37: 509–519, 1997.PubMedCrossRefGoogle Scholar
  7. Bondar, RJL, and Mead, DC: Evaluation of glucose-6-phosphate dehydrogenase from Leukonostoc mesenteroides in the hexokinase method for determining glucose in serum. Clin. Chem., 20:586–592, 1974.PubMedGoogle Scholar
  8. Busbee, D, Gauntt, C, Mouneimne, R, Burghardt, RC, McAnalley, and McDaniel, HR: Protection from glutathione depletion by a glyconutritional mixture of saccharides, J. Am. Aging Assoc. (Pending), 1999.Google Scholar
  9. Caggana, M, Chan, P, and Ramsingh, A: Identification of a single amino acid residue in the capsid protein VP1 of coxsackievirus B4 that determines the virulent phenotype. J. Virol., 67:4797–4803, 1993.PubMedGoogle Scholar
  10. Chatterjee, NK, Hou, J, Dockstader, P, and Charbonneau, T: Coxsackievirus B4 infection alters thymic, splenic, and peripheral lymphocyte repertoire preceding onset of hyperglycemia in mice. J. Med. Virol., 38:124–131, 1992.PubMedGoogle Scholar
  11. Cherry, JD: Enteroviruses, in Infectious Diseases of the Fetus and Newborn Infant, edited by Remington, JS, Klein, JD, 4th Ed., Philadelphia, W.B. Saunders, 1995, pp. 404–446.Google Scholar
  12. Dawson, TM, and Dawson, VL: Nitric oxide: actions and pathologic roles. Neuroscientist, 1:9–20, 1994.Google Scholar
  13. Freeman, G, Colston, J, Zabalgoitia, M, and Chandrasekar, B: Contractile depression and expression of proinflammatory cytokines and iNOS in viral myocarditis. Am. J. Physiol., 274:H249–H258, 1998.PubMedGoogle Scholar
  14. Gauntt, CJ: Roles of the humoral response in CVB-induced disease, in The Coxsackie B Viruses, Volume 223, Current Topics in Microbiology and Immunology, edited by Tracy, S, Chapman, N and Mahy, B, Berlin, Springer, 1997, pp. 259–282.Google Scholar
  15. Gauntt, CJ, Arizpe, HM, Higdon, AL, Wood, HJ, Bowers, DF, Rozek, MM, and Crawley, R: Molecular mimicry, anti-coxsackievirus B3 neutralizing monoclonal antibodies and myocarditis. J. Immunol., 154:2983–2995, 1995.PubMedGoogle Scholar
  16. Gauntt, CJ, Wood, HJ, McDaniel, HR, and McAnalley, BH: Aloe polymannose enhances anti-coxsackievirus antibody titers in mice. Phytotherapy Res., 14:1–6, 2000.CrossRefGoogle Scholar
  17. Godeny, EK, Arizpe, HM, and Gauntt, CJ: Characterization of the antibody response in vaccinated mice protected against coxsackievirus B3-induced myocarditis. Viral Immunol., 1:305–314, 1988.CrossRefGoogle Scholar
  18. Grendell, JH, and Egan, J: Acute pancreatitis. West J. Med., 146:598–602, 1987.Google Scholar
  19. Gu. D, Lee, M-S, Krahl, T, and Sarvetnick, N: Transitional cells in the regenerating pancreas. Development, 120:1873–1881, 1994.PubMedGoogle Scholar
  20. Hall, PA, and Lemoine, NR: Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas. J. Pathol., 166:97–103, 1992.PubMedCrossRefGoogle Scholar
  21. Hiraoka, Y, Kishimoto, C, Takada, H, Nakamura, M, Kurokawa, M, Ochiai, H, and Shiraki, K: Nitric oxide and murine coxsackievirus B3 myocarditis: aggravation of myocarditis by inhibition of nitric oxide synthetase. J. Am. Coll. Cardiol., 28:1610–1615, 1996.PubMedCrossRefGoogle Scholar
  22. Hirasawa, K, Jun, H, Maeda, K, Kawaguchi, Y, Itagaki, S, Mikami, T, Baek, H, Doi, K, and Yoon, J: Possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus induced diabetes in mice. J. Virol., 71:4024–4031, 1997.PubMedGoogle Scholar
  23. Hou, J, Said, C, Franchi, D, Dockstader, P, and Chatterjee, NK: Antibodies to glutamic acid decarboxylase and P2-C peptides in sera from coxsackie virus B4-infected mice and IDDM patients. Diabetes, 43:1260–1266, 1994.PubMedGoogle Scholar
  24. Huber, SA, Gauntt, CJ, and Sakkinen, P: Enteroviruses and myocarditis: viral pathogenesis through replication, cytokine induction and immunopathogenicity. Advances Virus Res., 51:35–63, 1998.Google Scholar
  25. Iovanna, JL, Lechene de la Porte, P, and Dagorn, J-C: Expression of genes associated with dedifferentiation and cell proliferation during pancreatic regeneration and following acute pancreatitis. Pancreas, 7:712–718, 1992.PubMedCrossRefGoogle Scholar
  26. Jones, DB, and Crosby, I: Proliferative lymphocyte responses to virus antigens homologous to GAD65 in IDDM. Diabetologia, 39:1318–1324, 1996.PubMedCrossRefGoogle Scholar
  27. Kuno, S, Itagaki, A, Yamazaki, I, Katsumoto, T, and Kurimura, T: Pathogenicity of newly isolated coxsackievirus B4 for mouse pancreas. Acta. Virol., 28:433–436, 1984.PubMedGoogle Scholar
  28. Lansdown, ABG: Pathological changes in the pancreas of mice following infection with coxsackie B virus. Br. J. Exp. Path., 57:331–338, 1976.Google Scholar
  29. Leach, SV, Gorelick, FS, and Modlin, IM: New perspectives on acute pancreatitis. Scand. J. Gastroenterol., 27:9–38, 1992.Google Scholar
  30. Lechene de la Porte, P, Iovanna, J, Odaira, C, Choux, R, Sarles, H, and Berger, Z: Involvement of tubular complexes in pancreatic regeneration after acute necrohemorrhagic pancreatitis. Pancreas, 6:298–306, 1991.PubMedGoogle Scholar
  31. Lonnrot, M, Hoyoty, H, Knip, M, Roivainen, M, Kulmala, P, Leinikki, P, and Akerblom, HK: Antibody cross-reactivity induced by the homologous regions in glutamic acid decarboxylase (GAD65) and 2C protein of coxsackievirus B4. Childhood Diabetes in Finland Study Group. Clin. Exp. Immunol., 104:398–405, 1996.PubMedCrossRefGoogle Scholar
  32. Lowenstein, C, Hill, S, Lafond-Walker, A, Wu, J, Allen, G, Landavere, M, Rose, N, and Herkowitz, A: Nitric oxide inhibits viral replication in murine myocarditis. J. Clin. Invest., 97:1837–1843, 1996.PubMedCrossRefGoogle Scholar
  33. Maxwell, SRJ: Prospects for the use of antioxidant therapies. Drugs, 49:345–361, 1995.PubMedGoogle Scholar
  34. McDaniel, CF, Dykman, KD, McDaniel, HR, Ford, CR, and Tone, CM: Effects of nutraceutical dietary intervention in diabetes mellitus: a retrospective survey. Proc. Fisher Inst. Med. Res., 1:19–23, 1997.Google Scholar
  35. Melnick, JL: Polioviruses and other enteroviruses, in Viral Infections of Humans. Epidemiology and Control, edited by Evans, AS, and Kaslow, RA, 4th Ed., New York, Plenum Medical, 1997, pp. 583–663.Google Scholar
  36. Pallansch, MA: Epidemiology of group B coxsackievirus, in Coxsackieviruses-A General Update, edited by Bendinelli, M, and Friedman, H, New York, Plenum, 1988, pp. 399–417.Google Scholar
  37. Pappenheimer, AM, Kunz, LJ, and Richardson, S: Passage of coxsackie virus (Connecticut-5 strain) in adult mice with production of pancreatic disease. J. Exp. Med., 94:45–64, 1951.PubMedCrossRefGoogle Scholar
  38. Ramsingh, A, and Collins, DN: A point mutation in the Vp4 coding sequence of coxsackievirus B4 influences virulence. J. Virol., 69:7278–7281, 1995.PubMedGoogle Scholar
  39. Ramsingh, A, Slack, J, Silkworth, J, and Hixon, A: Severity of disease induced by a pancreatropic coxsackie B4 virus correlates with the H-2K locus of the major histocompatibility complex. Virus Res., 14:347–358, 1989.PubMedCrossRefGoogle Scholar
  40. Reber, HA: Alcoholic pancreatitis, in Surgical Diseases of the Pancreas, edited by Howard, JM, Jordan, GL, and Reber, HA, Philadelphia, Lea and Febiger, 1987, pp. 284–296.Google Scholar
  41. Regan, PT, and Go, VLW: Pancreatic diseases, in Internal Medicine, edited by Stein, JH, 3rd Ed., Boston, Little, Brown and Co., 1990, pp. 546–556.Google Scholar
  42. Reiss, CS, and Komatsu, T: Does nitric oxide play a critical role in viral infections. Minireview. J. Virol., 72:4547–4551, 1998.Google Scholar
  43. Rice, GC, Bump, EA, Shrieve, DC, Kovacs, W, and Kovacs, M: Quantitative analysis of cellular glutathione by flow cytometry using monochlorobimane: some applications to radiation and drug resistance in vitro and in vivo. Cancer Res., 46:6105–6110, 1986.PubMedGoogle Scholar
  44. Ross, ME, Hayashi, K, and Notkins, AL: Virus-induced pancreatic disease: alterations in concentration of glucose and amylase in blood. J. Infect. Dis., 129:669–676, 1974.PubMedGoogle Scholar
  45. Shrieve, DC, Bump, EA, and Rice, GC: Heterogeneity of cellular glutathione among cells derived from a murine fibrosarcoma or a human renal cell carcinoma detected by flow cytometric analysis. J. Biol. Chem., 263: 14107–14114, 1988.Google Scholar
  46. Steer, ML, and Meldolesi, J: Pathogenesis of acute pancreatitis. Ann. Rev. Med., 39:95–105, 1988.PubMedCrossRefGoogle Scholar
  47. Tisch, R, Yang, S-D, Singer, SM, Liblau, RS, Fugger, L, and McDevitt, HO: Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature, 366:72–75, 1993.PubMedCrossRefGoogle Scholar
  48. Trousdale, MD, Paque, RE, and Gauntt, CJ: Assessment of coxsackievirus B3 ts mutants for induction of myocarditis in a murine model. Infect. Immun., 23:486–495, 1979.PubMedGoogle Scholar
  49. Webb, SR, and Madge, GE: The role of host genetics in the pathogenesis of coxsackievirus infection in the pancreas of mice. J. Inf. Dis., 141:47–54, 1980.Google Scholar

Copyright information

© American Aging Association, Inc. 1999

Authors and Affiliations

  • C. Gauntt
    • 1
  • D. Busbee
    • 2
  • H. J. Wood
    • 1
  • S. Reyna
    • 1
  • R. Barhoumi
    • 2
  • R. Burghardt
    • 2
  • W. McAnalley
    • 3
  • H. R. McDaniel
    • 3
  1. 1.Department of Microbiology, Mail Code 7758The University of Texas Health Science Center at San AntonioSan Antonio
  2. 2.Department of Anatomy and Public Health, College of Veterinary MedicineTexas A&M UniversityCollege Station
  3. 3.Research and Development (W.M.) or Medical (H.R.M.) DivisionsMannatech, Inc.Coppell

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