Protective effect of alpha-ketoglutarate against water-immersion restraint stress-induced gastric mucosal damage in mice

Eur J Pharmacol. 2023 Dec 5:960:176118. doi: 10.1016/j.ejphar.2023.176118. Epub 2023 Oct 21.


Gastric lesions have several aetiologies, among which stress is the most prominent. Therefore, identification of new therapies to prevent stress is of considerable importance. Alpha-ketoglutarate (α-kg) several beneficial effects and has shown promise in combating oxidative stress, inflammation, and premature aging. Thus, this study aimed to evaluate the protective effect of α-kg in a gastric damage model by water-immersion restraint stress (WIRS). Pretreatment with α-kg decreased stress-related histopathological scores of tissue oedema, cell loss, and inflammatory infiltration. The α-kg restored the percentage of type III collagen fibres. Mucin levels were preserved as well as the structure and area of the myenteric plexus ganglia were preserved after pretreatment with α-kg. Myeloperoxidase (MPO) levels and the expression of pro-inflammatory cytokines (TNF-α and IL-1β) were also reduced following α-kg pretreatment. Decreased levels of glutathione (GSH) in the stress group were restored by α-kg. The omeprazole group was used as standard drug e also demonstrated improve on some parameters after the exposition to WIRS as inflammatory indexes, GSH and mucin. Through this, was possible to observe that α-kg can protect the gastric mucosa exposed to WIRS, preserve tissue architecture, reduce direct damage to the mucosa and inflammatory factors, stimulate the production of type III collagen and mucin, preserve the myenteric plexus ganglia, and maintain antioxidant potential. Due to, we indicate that α-kg has protective activity of the gastric mucosa, demonstrating its ability to prevent damage associated with gastric lesions caused by stress.

Keywords: Alpha-ketoglutarate; Gastric damage; Gastric mucosa; Stress-induced mucosal damage.

MeSH terms

  • Animals
  • Collagen Type III / metabolism
  • Gastric Mucosa
  • Glutathione / metabolism
  • Immersion
  • Ketoglutaric Acids* / metabolism
  • Ketoglutaric Acids* / pharmacology
  • Ketoglutaric Acids* / therapeutic use
  • Mice
  • Mucins / metabolism
  • Restraint, Physical / adverse effects
  • Stomach Ulcer* / pathology
  • Water / metabolism


  • Ketoglutaric Acids
  • Collagen Type III
  • Glutathione
  • Mucins
  • Water