Effect of a zinc l-carnosine compound on acid-induced injury in canine gastric mucosa ex vivo

Tracy L. Hill Department of Clinical Science, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Anthony T. Blikslager Department of Clinical Science, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Abstract

Objective—To examine whether a zinc l-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa.

Sample—Gastric mucosa from 6 healthy dogs.

Procedures—Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc l-carnosine compound, or zinc l-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti–active caspase-3 antibody as an indicator of apoptosis.

Results—Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc l-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc l-carnosine compound did not protect against development of apoptosis.

Conclusions and Clinical Relevance—Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc l-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.

Abstract

Objective—To examine whether a zinc l-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa.

Sample—Gastric mucosa from 6 healthy dogs.

Procedures—Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc l-carnosine compound, or zinc l-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti–active caspase-3 antibody as an indicator of apoptosis.

Results—Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc l-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc l-carnosine compound did not protect against development of apoptosis.

Conclusions and Clinical Relevance—Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc l-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.

Contributor Notes

Presented as an oral presentation at the 28th Annual American College of Veterinary Internal Medicine Forum, Anaheim, Calif, June 2010.

Address correspondence to Dr. Blikslager (Anthony_Blikslager@ncsu.edu).
  • 1.

    Hinton LE, McLoughlin MA, Johnson SE, et al. Spontaneous gastroduodenal perforation in 16 dogs and seven cats (1982–1999). J Am Anim Hosp Assoc 2002; 38:176187.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Jergens AE, Moore FM, Haynes JS, et al. Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987–1990). J Am Vet Med Assoc 1992; 201:16031608.

    • Search Google Scholar
    • Export Citation
  • 3.

    Kavitha S, Prathaban S, Vasu K, et al. Endoscopic isolation of Helicobacter pylori from gastric ulcer dogs. Indian J Vet Med 2007; 27:14.

    • Search Google Scholar
    • Export Citation
  • 4.

    Stanton ME, Bright RM. Gastroduodenal ulceration in dogs retrospective study of 43 cases and literature review. J Vet Intern Med 1989; 3:238244.

    • Search Google Scholar
    • Export Citation
  • 5.

    Lascelles BDX, Blikslager AT, Fox SM, et al. Gastrointestinal tract perforation in dogs treated with a selective cyclooxy-genase-2 inhibitor: 29 cases (2002–2003). J Am Vet Med Assoc 2005; 227:11121117.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Baan M, Sherding RG, Johnson SE. Effects of zinc-l-carnosine and vitamin E on aspirin-induced gastrointestinal injury in dogs. J Vet Intern Med 2011; 25:3946.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Teva Animal Health. Gastricalm product details. Available at: www.tevaanimalhealth.com/Products/ProductDetails.aspx?productId=aeaa3a22-1c86-4777-9baa-134f3b4d3614. Accessed Jul 14, 2008.

  • 8.

    Hiraishi H, Sasai T, Oinuma T, et al. Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro. Aliment Pharmacol Ther 1999; 13:261269.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Fuji Y, Matsura T, Kai M, et al. Protection by polaprezinc, an anti-ulcer drug, against indomethacin-induced apoptosis in rat gastric mucosal cells. Jpn J Pharmacol 2000; 84:6370.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Mahmood A, FitzGerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut 2007; 56:168175.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Naito Y, Yoshikawa T, Yagi N, et al. Effects of polaprezinc on lipid peroxidation, neutrophil accumulation, and TNF-alpha expression in rats with aspirin-induced gastric mucosal injury. Dig Dis Sci 2001; 46:845851.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Kato S, Tanaka A, Ogawa Y, et al. Effect of polaprezinc on impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats—role of insulin-like growth factors (IGF)-1. Med Sci Monit 2001; 7:2025.

    • Search Google Scholar
    • Export Citation
  • 13.

    Mikami K, Otaka M, Watanabe D, et al. Zinc l-carnosine protects against mucosal injury in portal hypertensive gastropathy through induction of heat shock protein 72. J Gastroenterol Hepatol 2006; 21:16691674.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Hayakawa A, Inoue M, Kunizaki M, et al. Clinical evaluation of Z-103 on gastric ulcer. Jpn Pharmacol Ther 1992; 20:255264.

  • 15.

    Korolkiewicz RP, Fujita A, Seto K, et al. Polaprezinc exerts a salutary effect on impaired healing of acute gastric lesions in diabetic rats. Dig Dis Sci 2000; 45:12001209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Odashima M, Otaka M, Jin M, et al. Induction of a 72-kDa heat-shock protein in cultured rat gastric mucosal cells and rat gastric mucosa by zinc l-carnosine. Dig Dis Sci 2002; 47:27992804.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Odashima M, Otaka M, Jin M, et al. Zinc l-carnosine protects colonic mucosal injury through induction of heat shock protein 72 and suppression of NF-kB activation. Life Sci 2006; 79:22452250.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Sagawa K, Li F, Liese R, et al. Fed and fasted gastric pH and gastric residence time in conscious Beagle dogs. J Pharm Sci 2009; 98:24942500.

  • 19.

    Youngberg CA, Wlodyga J, Schmaltz S, et al. Radiotelemetric determination of gastrointestinal pH in four healthy Beagles. Am J Vet Res 1985; 46:15161521.

    • Search Google Scholar
    • Export Citation
  • 20.

    Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 2008; 135:4160.

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