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Co-lyophilized Aspirin with Trehalose Causes Less Injury to Human Gastric Cells and Gastric Mucosa of Rats

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Abstract

Background

Aspirin is one of the most popular NSAIDs worldwide because of its anti-inflammatory and anticoagulant effects, and however, gastrointestinal injury remains a major complication. We previously reported co-lyophilized aspirin/trehalose (Lyo A/T) decreased the aspirin-induced gastric lesions in dogs.

Aim

This study investigated the mechanism of gastroprotective effects of trehalose in vitro and in vivo.

Methods

The apoptotic assays were performed in a human gastric carcinoma cell line, which was treated with aspirin, mixed aspirin/trehalose (Mix A/T) or Lyo A/T. Gastric ulcer severity was examined after oral administration of drugs in rats. In addition, the mucosal tissue apoptotic status in drug-treated rats was evaluated. Molecular dynamics simulations and laser Raman spectroscopy were performed in order to examine the molecular properties of Lyo A/T.

Results

DNA fragmentation was detected in AGS cells that were treated with aspirin and Mix A/T, but not in the Lyo A/T-treated cells. There were fewer apoptotic cells in the Lyo A/T-treated cells than in the other cells. Gastric injury was reduced in rats that received oral Lyo A/T compared with the others, while PGE2 synthesis was equally decreased in all groups. TUNEL assay and immunohistochemistry of cleaved caspase-3 in the mucosal tissues also revealed that Lyo A/T treatment induced less apoptosis than the others. The Lyo A/T spectrum showed clear differences in several Raman bands compared with that of Mix A/T.

Conclusions

Our data showed that co-lyophilization of aspirin with trehalose reduced gastric injury, potentially through suppression of aspirin-induced mucosal cell apoptosis while retaining its anti-inflammatory effects.

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Acknowledgments

We thank Tohru Kanke for his technical assistance. The present work was supported by JSPS KAKENHI Grant Numbers 21650105 and 25750156 and by the Platform Project for Supporting in Drug Discovery and Life Science Research from Japan Agency for Medical Research and Development (AMED).

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    Authors and Affiliations

    1. Department of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Taiwan

      Lee-Shuan Lin

    2. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

      Yuko Kayasuga-Kariya, Takamasa Sakai, Ayano Fujisawa, Yuki Akagi & Ung-il Chung

    3. Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan

      Shugo Nakamura

    4. Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

      Nobuyuki Shimohata

    5. NEXT21 K.K., 3-38-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

      Shigeki Suzuki

    6. Department of Veterinary Medical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan

      Nobuo Sasaki & Manabu Mochizuki

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    1. Lee-Shuan Lin
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    Correspondence to Manabu Mochizuki.

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    Lee-Shuan Lin and Yuko Kayasuga-Kariya have contributed equally to this work.

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    Lin, LS., Kayasuga-Kariya, Y., Nakamura, S. et al. Co-lyophilized Aspirin with Trehalose Causes Less Injury to Human Gastric Cells and Gastric Mucosa of Rats. Dig Dis Sci 61, 2242–2251 (2016). https://doi.org/10.1007/s10620-016-4209-z

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