Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves

Konturek, S.J., Zayachkivska, O., Havryluk, X.O., Brzozowski, T., Sliwowski, Z., Pawlik, M., Konturek, P.C., Czesnikiewicz-Guzik, M. , Gzhegotsky, M.R. and Pawlik, W.W. (2007) Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves. Journal of Physiology and Pharmacology, 58(2), pp. 361-377.

Abstract

Melatonin (MT) is known to protect gastrointestinal mucosa against various types of injury but its effects on esophageal damage have not been studied. We examined the effects of MT on acute esophageal injury and the mechanism involved in the action of this indole. Acute esophageal lesions were induced by perfusion with acid-pepsin solution using tube inserted through the oral cavity into the mid of esophagus of anaesthetized rats with or without inhibition of prostaglandin (PG) generation by indomethacin (5 mg/kg/day), nitric oxide (NO) formation by NG-nitro-L-arginine (L-NNA, 20 mg/kg/day) or sensory nerves deactivation by capsaicin (125 mg/kg, sc). The esophageal injury was assessed by macroscopic score and histologic activity index. The esophageal mucosal blood flow (EBF) was determinated by H2-gas clearance method. The plasma TNF-alpha and nitrate/nitrite (NOx) levels and mucosal PGE2 contents were assessed by immunoassays. Esophageal acid-pepsin perfusion induced noticeable esophageal mucosal injury as compared to perfusion with vehicle saline. The pretreatment with MT prevented significantly esophageal injury, raised EBF and mucosal content of PGE2, while decreasing the levels of TNF-alpha. Inhibition of COX/PG and NOS/NO systems by indomethacin and L-NNA, respectively, or inactivation of sensory nerves by capsaicin, that manifested in further increase of esophageal injury, reduced the levels of EBF, markedly raised the levels TNF-alpha and reduced mucosal PGE2, but the pretreatment with MT prevented significantly esophageal injury, improved EBF and raised mucosal PGE2 contents. These studies suggest that MT can be considered as a novel esophagoprotector, acting, at least in part, through the COX/PG and NOS/NO systems and activation of sensory nerves.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Czesnikiewicz-Guzik, Dr Marta
• Authors: Konturek, S.J., Zayachkivska, O., Havryluk, X.O., Brzozowski, T., Sliwowski, Z., Pawlik, M., Konturek, P.C., Czesnikiewicz-Guzik, M., Gzhegotsky, M.R., and Pawlik, W.W.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Journal of Physiology and Pharmacology
• ISSN: 0867-5910
• ISSN (Online): 1899-1505