Boric Acid Alleviates Gastric Ulcer by Regulating Oxidative Stress and Inflammation-Related Multiple Signaling Pathways

Biol Trace Elem Res. 2024 May;202(5):2124-2132. doi: 10.1007/s12011-023-03817-7. Epub 2023 Aug 22.

Abstract

Oxidative stress and inflammation have pivotal roles in gastric ulcer development caused by alcohol consumption. Trace element boric acid taken into the human and animal body from dietary sources displays strong antioxidant and anti-inflammatory functions. However, the mechanisms underlying these actions of boric acid remain unclear, and its effectiveness in preventing gastric lesions is unknown. Therefore, the present study was undertaken to evaluate the protective effects of boric acid in alcohol-induced gastric ulcer and elucidate its potential mechanisms. Gastric ulcer was induced by 75% oral ethanol administration in rats, and the effectiveness of prophylactic boric acid treatment at 100 mg/kg concentration was assessed by histopathological examination, ELISA assay and qRT-PCR. Gross macroscopic and histopathological evaluations revealed that boric acid alleviated gastric mucosal lesions. Boric acid decreased reactive oxygen species (ROS) and malondialdehyde (MDA) concentration and the overall oxidation state of the body while improving antioxidant status. It reduced the concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The mRNA expression of JAK2 and STAT3 was decreased while the expression of AMPK was increased with boric acid pretreatment. Moreover, Sema3A and PlexinA1 levels were elevated upon boric acid pretreatment, and homocysteine levels were reduced. Our results demonstrated that boric acid protects gastric mucosa from ethanol-induced damage by regulating oxidative and inflammatory responses. In addition, our findings suggested that the gastroprotective activity of boric acid could be attributed to its regulatory function in the IL-6/JAK2/STAT3 signaling modulated by AMPK and that Sema3A/PlxnA1 axis and homocysteine are potentially involved in this process.

Keywords: AMPK; Gastric ulcer; Homocysteine; IL-6/JAK2/STAT3 pathway; Inflammation; Sema3A/PlexinA1.

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Anti-Ulcer Agents* / pharmacology
  • Anti-Ulcer Agents* / therapeutic use
  • Antioxidants / metabolism
  • Boric Acids*
  • Ethanol / adverse effects
  • Gastric Mucosa
  • Homocysteine / metabolism
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Oxidative Stress
  • Rats
  • Semaphorin-3A / metabolism
  • Semaphorin-3A / pharmacology
  • Semaphorin-3A / therapeutic use
  • Signal Transduction
  • Stomach Ulcer* / chemically induced
  • Stomach Ulcer* / drug therapy
  • Stomach Ulcer* / prevention & control

Substances

  • Antioxidants
  • boric acid
  • Interleukin-6
  • AMP-Activated Protein Kinases
  • Semaphorin-3A
  • Anti-Ulcer Agents
  • Ethanol
  • Homocysteine
  • Boric Acids