Gastroprotective effect of dalargin in gastropathy due to treatment with nonsteroid antiinflammatory drugs

This Russian study, conducted at the Far Eastern State Medical University in Khabarovsk, investigated the gastroprotective effect of dalargin in a clinically relevant experimental model: non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy. NSAID gastropathy remains one of the main iatrogenic causes of peptic ulcer and upper gastrointestinal bleeding, especially in elderly polypharmacy patients.

The researchers administered indomethacin to rats to induce acute gastric mucosal lesions and tested the ability of dalargin (a synthetic leu-enkephalin analog with selectivity for peripheral delta-opioid receptors) to protect the stomach. The dalargin-treated group was compared to controls, and the gastric mucosa was evaluated by histology, cell proliferation markers, and biochemical parameters of oxidative stress.

Results demonstrated three main protective effects: (1) significant reduction in total erosive and ulcerative lesion area in the stomach; (2) normalization of mucosal epithelial cell proliferation, reflecting recovery of regenerative capacity; (3) decreased mucosal oxidative stress, measured by lipid peroxidation markers. Interestingly, a structural analog ([Dala]2-leu-enkephalin) lacking the C-terminal arginine residue did not show this effect, suggesting that the complete hexapeptide structure is required for gastroprotection.

This work provided robust mechanistic evidence for the clinical use of dalargin as a gastroprotective agent, especially in contexts where NSAIDs are essential. It reinforced the concept that peripheral delta-opioid receptor activation represents a pharmacological strategy for gastrointestinal mucosal preservation, with a more favorable safety profile than central opioid analogs.