The newer therapeutic alternatives to the acid‐oriented approach via targeting endothelial metabolism in esophagoprotection by 5‐hydroxytryptamine (5‐HP) and melatonin (MT)

Abstract

Existing treatment of erosive and nonerosive esophagitis (NEE) which incidence has risen dramatically in recent years are mostly based on potent acid suppression. Modern data revealed that the prolonged acid suppression is associated with dismotility in foregut, extraesophageal disorders, abnormal microbiota, and induction selective apoptosis for cancer. We hypothesized that endothelial metabolism is key in multifactorial esophageal mucosa (EM) defense and studied 5‐HT/MT specific effects on EM endothelial metabolism during NEE associated to stress model (WRS) and 28 days of postprandial hyperglycemia (PPH) in rats was studied without/with 5‐HT (100 mg/kg) and MT (20 mg/kg) via VEGF, EGF, IL‐1β, TNFα synthesis by ELISA; EM injury via histological score index (HSI); functional reorganization of microangioarchitecture by mannose specific labeling.ResultsNNE constantly increased HSI in 150% in binary PPH and WRS; 5‐HT/MT decreased HIS 38% & 57%, respectively; potent MT and 5‐HT modulation vascular tone were through VEGF, TNFα synthesis better then 5‐HT. Changes in alfa‐DMan>;D‐Gal EM expression confirmed key role of endothelial metabolism in NEE and MT decreased expression of endothelial dysfunction. We concluded that MT has potent esophagoprotective effect then 5‐HT via decreasing endothelial permeability, thus may be alternative to the acid‐orientated approach.