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Α-Ketoglutarate ameliorates appendicitis by modulating Gln metabolism and inhibiting NF - κB signaling pathway - PubMed

4 hours ago
  • #acute-appendicitis
  • #nf-kb-signaling
  • #glutamine-metabolism
  • α-Ketoglutarate (α-KG) improves appendicitis by regulating Glutamine (Gln) metabolism and inhibiting the NF-κB signaling pathway.
  • Acute appendicitis involves dysregulated immune responses and metabolic disturbances, with current treatments limited by complications and recurrence risks.
  • Inflamed appendiceal tissues showed downregulation of Gln catabolic genes (GLS1, GLUD1) and reduced α-KG levels, linked to NF-κB hyperactivation and cytokine storms.
  • Exogenous α-KG supplementation in murine models suppressed p65 phosphorylation, stabilized IκBα, and reduced pro-inflammatory cytokines (IL-6, TNF-α), improving survival rates.
  • Combined α-KG and antibiotic therapy showed synergistic effects, while Gln alone had limited benefits.
  • Dysfunctional Gln metabolism contributes to appendicitis pathogenesis via NF-κB-mediated inflammation, with α-KG showing potential as an adjunctive therapy.