Caffeic acid attenuates gastric mucosal damage induced by ethanol in rats via nitric oxide modulation

Chem Biol Interact. 2021 Jan 25:334:109351. doi: 10.1016/j.cbi.2020.109351. Epub 2020 Dec 8.

Abstract

Anti-oxidant and anti-inflammatory properties of caffeic acid (CA) have been reported recently. In this study, the therapeutic effects of CA on ethanol-induced ulcer and the roles of nitric oxide and cholinergic pathways in these effects were investigated. Ulcer was induced by ethanol via oral gavage. Ulcer induced rats were treated with either vehicle (ulcer group) or CA (100, 250 or 500 mg/kg, per oral gavage). Macroscopic evaluation showed that 250 mg/kg CA was the effective dose. To elucidate the action mechanism of CA, 10 mg/kg l-NAME or 1 mg/kg atropine sulfate was administered to 250 mg/kg CA treated groups. All rats were decapitated 1 h after ulcer induction and gastric samples were scored macroscopically and microscopically, and analyzed for myeloperoxidase (MPO), malondialdehyde (MDA), and glutathione (GSH) levels. ANOVA test was used for statistical analyses. Macroscopic and microscopic damage scores, MDA levels and MPO activity were increased while GSH levels were decreased in ulcer group. Treatment with 250 mg/kg and 500 mg/kg CA reduced macroscopic and microscopic damage scores, decreased MPO activity and MDA levels, and preserved the depleted glutathione significantly. l-NAME administration before CA treatment elevated MDA levels, MPO activity and depleted glutathione. However, atropine sulfate had no effect on biochemical parameters. We conclude that CA ameliorates ethanol-induced gastric mucosal damage, and NO pathway contributes to this effect. On the other hand, there is a lack of evidence for the contribution of the muscarinic cholinergic system.

Keywords: Anti-oxidant; Caffeic acid; Cholinergic; Nitric oxide; Ulcer.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Ulcer Agents / pharmacology
  • Antioxidants / metabolism
  • Caffeic Acids / pharmacology*
  • Cholinergic Agents / pharmacology
  • Disease Models, Animal
  • Ethanol / pharmacology*
  • Gastric Mucosa / diagnostic imaging*
  • Gastric Mucosa / metabolism
  • Glutathione / metabolism
  • Male
  • Malondialdehyde / metabolism
  • NG-Nitroarginine Methyl Ester / metabolism
  • Nitric Oxide / metabolism*
  • Peroxidase / metabolism
  • Phytotherapy / methods
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Ulcer / chemically induced*
  • Stomach Ulcer / drug therapy*
  • Stomach Ulcer / metabolism

Substances

  • Anti-Inflammatory Agents
  • Anti-Ulcer Agents
  • Antioxidants
  • Caffeic Acids
  • Cholinergic Agents
  • Plant Extracts
  • Nitric Oxide
  • Ethanol
  • Malondialdehyde
  • Peroxidase
  • Glutathione
  • caffeic acid
  • NG-Nitroarginine Methyl Ester