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

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...

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Published in:European journal of pharmacology 2023-12, Vol.960, p.176118-176118, Article 176118
Main Authors: Lopes, André Luis Fernandes, Araújo, Andreza Ketly da Silva, Chaves, Letícia de Sousa, Pacheco, Gabriella, Oliveira, Ana Patrícia de, Silva, Katriane Carvalho da, Oliveira, Antonio Carlos Pereira de, Aquino, Cristhyane Costa de, Gois, Marcelo Biondaro, Nicolau, Lucas Antonio Duarte, Medeiros, Jand Venes Rolim
Format: Article
Language:English
Subjects:
Alpha-ketoglutarate
Gastric damage
Gastric mucosa
Stress-induced mucosal damage
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Summary: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. •Ketoglutarate (α-kg) protects against stress-induced gastric injury in murine model.•Formerly raised TNF-α and IL-1β levels greatly attenuated by treating with α-kg.•Group supplemented with α-kg had higher mucin levels in the gastric mucosa.•α-kg restored mucin levels in gastric mucosa and restored glutathione levels.•α-kg also has role in sustaining area and structure of myenteric plexus ganglia.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2023.176118