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Chemical Structure of Bismuth Compounds Determines Their Gastric Ulcer Healing Efficacy and Anti- Helicobacter pylori Activity

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Abstract

The recognition of the role of Helicobacterpylori in the pathogenesis of peptic ulcer disease hasled to renewed interest in bismuth pharmacology sincebismuth compounds have both anti-Helicobacter pylori and ulcer healing properties. The precisechemical structure of current bismuth compounds is notknown. This has hindered the development of new andpotentially more efficacious formulations. We havecreated two new compounds,2-chloro1,3-dithia-2-bismolane (CDTB) and1,2-[bis(1,3-dithia-2-bismolane)thio]ethane (BTBT), withknown structure. In a rat model of gastric ulceration,BTBT was comparable to, and CDTB was significantly less effective thancolloidal bismuth subcitrate in healing cryoprobeinducedulcers. However, both BTBT and CDTB inhibited H. pylorigrowth in vitro at concentrations <1/10 that of colloidal bismuth subcitrate. The effects onulcer healing are not mediated by suppression of acidsecretion, pepsin inhibition, or prostaglandinproduction. Since all treated animals received the same amount of elemental bismuth, it appears thatthe efficacy of bismuth compounds varies with compoundstructure and is not simply dependent on the delivery ofbismuth ion. Because the structure of the novel compounds is known, our understanding of therelationship of bismuth compound structure and tobiologic activity will increase. In the future it may bepossible to design other novel bismuth compounds with more potent anti-H. pylori and ulcer healingeffects.

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Authors
  1. Gurpal S. Sandha
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  2. Robin Leblanc
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  3. Sander J. O. Veldhuyzen Van Zanten
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  4. Troy D. Sitland
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  5. Lisa Agocs
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  6. Neil Burford
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  7. Linda Best
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  8. David Mahoney
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  9. Paul Hoffman
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  10. Desmond J. Leddin
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Sandha, G.S., Leblanc, R., Van Zanten, S.J.O.V. et al. Chemical Structure of Bismuth Compounds Determines Their Gastric Ulcer Healing Efficacy and Anti- Helicobacter pylori Activity. Dig Dis Sci 43, 2727–2732 (1998). https://doi.org/10.1023/A:1026667714603

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  • DOI: https://doi.org/10.1023/A:1026667714603

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