Ultra-structural study of the indomethacin-induced apoptosis and autophagy in rat gastric parietal cells

ABSTRACT

Background and aim of the work

Indomethacin (IND), a non-steroidal anti-inflammatory drug, can induce gastric mucosal ulcerations. To date, the ultra-structural changes in the parietal cells (PCs) of the gastric mucosa following the intake of IND are mostly unknown. We carried out the current investigation to get insights into this issue.

Materials and methods

We established an animal model consisting of 35 adult male Sprague Dawley rats. The animals were divided into three groups, including; control (normal feeding), fasting, and indomethacin-treated groups. After treatment of 18-h fasting rats with IND, they were sacrificed at 3, 6, and 12-h intervals. The morphological features, including the apoptotic, and autophagic changes in the gastric mucosa PCs were examined using transmission electron microscopy.

Results

In normal feeding animals (control group), the gastric PCs were present in various stages of activity. Fasting was associated with the predominance of the inactive parietal cells with features of up-regulated autophagy. In the IND -treated animals (at 3-h interval), PCs showed prominent autophagic changes, and subtle apoptotic cell death. In the IND -treated animals (at 6–12-h interval), PCs showed prominent apoptotic changes, and subtle autophagic features.

Conclusions

Our study indicates that IND treatment could induce gastropathy through time-dependent alterations in the autophagic and apoptotic machinery of PCs. Further studies are needed to examine the underlying molecular mechanisms.

KEYWORDS:

• Indomethacin
• apoptosis
• autophagy
• gastric mucosa
• parietal cells