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

• Published in: Digestive diseases and sciences Vol. 61; no. 8; pp. 2242 - 2251
• Main Authors: Lin, Lee-Shuan, Kayasuga-Kariya, Yuko, Nakamura, Shugo, Shimohata, Nobuyuki, Sakai, Takamasa, Fujisawa, Ayano, Akagi, Yuki, Suzuki, Shigeki, Chung, Ung-il, Sasaki, Nobuo, Mochizuki, Manabu
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2016; Springer; Springer Nature B.V
• Subjects: Animals; Anticoagulants (Medicine); Apoptosis; Apoptosis - drug effects; Aspirin; Aspirin - adverse effects; Aspirin - pharmacology; Biochemistry; Caspase 3 - drug effects; Caspase 3 - metabolism; Cell Line, Tumor; Epithelial Cells - drug effects; Freeze Drying; Gastric Mucosa - cytology; Gastric Mucosa - drug effects; Gastroenterology; Hepatology; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Male; Medicine; Medicine & Public Health; Molecular dynamics; Molecular Dynamics Simulation; Oncology; Original Article; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - pharmacology; Protective Agents - pharmacology; Raman spectroscopy; Rats; Rats, Sprague-Dawley; Spectrum Analysis, Raman; Stomach cancer; Stomach Ulcer - chemically induced; Transplant Surgery; Trehalose - pharmacology; Gastroprotection; Aspirin; Lyophilization; Trehalose; Apoptosis
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-016-4209-z

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 PGE 2 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.