Clinoptilolite in Dextran Sulphate Sodium-Induced Murine Colitis: Efficacy and Safety of a Microparticulate Preparation

Inflamm Bowel Dis. 2017 Dec 19;24(1):54-66. doi: 10.1093/ibd/izx042.

Abstract

Background: Clinoptilolite is an aluminium silicate of natural origin; the microporous structure and the net negative charge of its crystal lattice allows for adsorption of ions, toxins, inflammatory mediators, and some microorganisms. We generated 2 preparations of purified clinoptilolite, which differed by about 10-fold in particle size, ie, a standard powder (GHC1) and a microparticulate fraction (GHC2) with a size of 3.6 µm and 0.39 µm (d50) respectively. These were examined for their ability to accelerate the recovery of mice from DSS (dextran sulphate sodium)-induced intestinal inflammation.

Methods: Efficacy of clinoptilolite preparations was investigated by administering DSS-treated mice twice daily with 30 mg GHC2 or GHC1 for 5 consecutive days, followed by 5 days of recovery without DSS. To explore the safety of the microparticulate preparation (GHC2), mice were subjected to 4 cycles of DSS-exposure. We specifically verified that clinoptilolite microparticles were not systemically bioavailable by examining the gut tissue and the liver for the accumulation of microparticles by transmission electron microscopy.

Results: Treatment of mice with GHC2 was superior to GHC1 and as effective as the reference compound 5-aminosalicylic acid in ameliorating the damage induced by the exposure to DSS. In addition, no clinoptilolite particle was observed in the intestinal epithelial layer, gut-associated lymph follicles, or in the liver.

Conclusion: Our observations confirm that a microparticulate preparation of clinoptilolite is safe and effective in a murine model of inflammatory bowel disease and supports the hypothesis that the adsorptive capacity of clinoptilolite is of potential therapeutic relevance.

Keywords: DSS; colitis; inflammation; zeolite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / pathology
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity*
  • Disease Models, Animal*
  • Drug Compounding*
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome
  • Inflammation / microbiology
  • Inflammation / prevention & control*
  • Intestinal Diseases / microbiology
  • Intestinal Diseases / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Safety
  • Zeolites / administration & dosage
  • Zeolites / chemistry
  • Zeolites / pharmacology*

Substances

  • Cytokines
  • clinoptilolite
  • Zeolites
  • Dextran Sulfate