Carvedilol safeguards against aspirin-induced gastric damage in rats

Hum Exp Toxicol. 2020 Sep;39(9):1257-1267. doi: 10.1177/0960327120918306. Epub 2020 Apr 15.


This study investigated the effect of carvedilol on aspirin-induced gastric damage. Male Wistar rats were divided into three groups. Control rats received the vehicle, while the aspirin group received aspirin (200 mg/kg) orally for 4 days. Rats of aspirin + carvedilol group were administered aspirin along with carvedilol (5 mg/kg; intraperitoneal) for 4 days. Animals were euthanized at the end of the treatment period, and gastric tissues were collected to perform histopathological and mechanistic studies. The results revealed that aspirin administration induced gastric ulcer as there were remarkable histopathological lesions in the form of marked necrosis, inflammation, hemorrhage, edema, and dysplastic changes. Lipid peroxidative markers such as malondialdehyde, 4-hydroxynonenal, and protein carbonyl were significantly elevated in the aspirin group. This was concurrent with a significant amelioration of antioxidants such as reduced glutathione, superoxide dismutase, and catalase. Furthermore, aspirin increased the immunoexpression of cyclooxygenase (COX) 2 and nuclear factor kappa-B (NF-κB). Aspirin induced elevation in the inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Aspirin enhanced the immunoexpression of inducible nitric oxide synthetase (iNOS) and increased the level of nitrite/nitrate in gastric tissue. On the other hand, carvedilol treatment reversed all these pathological changes. Carvedilol succeeded to enhance antioxidants in gastric tissue, attenuated lipid peroxidative parameters, and suppressed the release of inflammatory mediators. It attenuated the immunoexpression of COX-2, NF-κB, and iNOS. Collectively, carvedilol has a gastro-protective effect that could be attributed to its antioxidative and anti-inflammatory properties, which modulate NF-κB/COX-2/iNOS pathways.

Keywords: Carvedilol; NF-κB; inflammation; oxidative stress; ulcer.

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacology
  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Carvedilol / administration & dosage*
  • Carvedilol / pharmacology
  • Cytokines / analysis
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Stomach Ulcer / chemically induced*
  • Stomach Ulcer / prevention & control*


  • Adrenergic beta-Antagonists
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Cytokines
  • Carvedilol
  • Aspirin