title: Vanillyl nonanoate protects rat gastric mucosa from ethanol-induced injury through a mechanism involving calcitonin gene-related peptide.
abstract: Previous studies have demonstrated that capsaicin-sensitive sensory nerves are involved in the protection of gastric mucosa against damage by various stimuli and calcitoin gene-related peptide (CGRP) is a potential mediator in this process. This study was performed to explore the effect of vanillyl nonanoate, a capsaicin analog, on ethanol-induced gastric mucosal injury and the possible underlying mechanisms. A rat model of gastric mucosal injury was induced by oral administration of acidified ethanol and gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, the activities of caspase-3, catalase and superoxide dismutase (SOD), levels of CGRP, TNF-α and malondialdehyde (MDA). The results showed that acute administration of ethanol significantly increased gastric ulcer index concomitantly with increased cellular apoptosis, caspase-3 activity, TNF-α and MDA levels as well as decreased activities of catalase and SOD. Pretreatment with 1mg/kg vanillyl nonanoate significantly attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by increase of CGRP expression, and SOD activity and decrease of caspase-3 activity, TNF-α and MDA levels. The effects of vanillyl nonanoate were inhibited by capsazepine, an antagonist of capsaicin receptor. Our results suggested that vanillyl nonanoate was able to protect the gastric mucosa against ethanol-induced gastric mucosal injury. The underlying mechanism is related to stimulation of CGRP release and subsequent suppression of ethanol-induced inflammatory reaction, cellular apoptosis and oxidative stress.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Xiu-Ju
authors.initials: XJ
authors.lastname: Luo
authors.forename: Nian-Sheng
authors.initials: NS
authors.lastname: Li
authors.forename: Yi-Shuai
authors.initials: YS
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Zhi-Chun
authors.initials: ZC
authors.lastname: Yang
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
authors.forename: Xin-Rong
authors.initials: XR
authors.lastname: Dong
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects*; D005227:Fatty Acids / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014641:Vanillic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D014409:Tumor Necrosis Factor-alpha; C508530:vanillyl nonanoate; D000431:Ethanol; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D014641:Vanillic Acid; D015740:Calcitonin Gene-Related Peptide