title: Co-lyophilized Aspirin with Trehalose Causes Less Injury to Human Gastric Cells and Gastric Mucosa of Rats.
abstract: 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.
  
  
  
  This study investigated the mechanism of gastroprotective effects of trehalose in vitro and in vivo.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Taiwan.
authors.forename: Lee-Shuan
authors.initials: LS
authors.lastname: Lin
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kayasuga-Kariya
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimohata
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Fujisawa
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Akagi
authors.affiliation: NEXT21 K.K., 3-38-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Ung-Il
authors.initials: UI
authors.lastname: Chung
authors.affiliation: 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.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: 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. amm@mail.ecc.u-tokyo.ac.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects*; D005612:Freeze Drying; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D056004:Molecular Dynamics Simulation; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013059:Spectrum Analysis, Raman; D013276:Stomach Ulcer / Q000139:chemically induced; D014199:Trehalose / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D020011:Protective Agents; D014199:Trehalose; C505410:Casp3 protein, rat; D053148:Caspase 3; D001241:Aspirin
keywords: Apoptosis; Aspirin; Gastroprotection; Lyophilization; Trehalose