Low-dose cyclooxygenase-2 (COX-2) inhibitor celecoxib plays a protective role in the rat model of neonatal necrotizing enterocolitis

Bioengineered. 2021 Dec;12(1):7234-7245. doi: 10.1080/21655979.2021.1980646.

Abstract

This study aims to investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor celecoxib on neonatal necrotizing enterocolitis (NEC) in rats. After treatment with a low dose of celecoxib (0.5, 1, or 1.5 mg/kg), pathological changes in the ileum and the levels of oxidative stress and inflammatory factors in NEC rats were compared. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors, terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) staining was employed to assess apoptotic epithelial cells in the ileum, and real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to quantify gene and protein expression, respectively. The incidences of NEC rats in the 0.5, 1 and 1.5 mg/kg celecoxib groups were lower than in the model group (100%). Celecoxib improved the histopathology of the ileum in NEC rats. Moreover, low doses of celecoxib relieved oxidative stress and inflammation in NEC rats, as evidenced by decreased tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), total oxidation state (TOS), malondialdehyde (MDA) and oxidative stress index (OSI), as well as increased interleukin-10 (IL-10), total antioxidant status (TAS), superoxide dismutase (SOD) and glutathione peroxidase (GPx). With increasing celecoxib doses (0.5, 1, or 1.5 mg/kg), the amount of apoptotic epithelial cells in the ileum of NEC rats gradually declined and Caspase-3 expression was reduced. The low dose of the COX-2 inhibitor celecoxib ameliorated the histopathologic conditions of the ileum, alleviated oxidative stress and inflammation, and reduced apoptotic epithelial cells in NEC rats, thereby making it a potential therapy for NEC.

Keywords: Necrotizing enterocolitis; celecoxib; cox-2.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Celecoxib / pharmacology*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Disease Models, Animal
  • Enterocolitis, Necrotizing* / metabolism
  • Enterocolitis, Necrotizing* / pathology
  • Ileum / drug effects
  • Ileum / pathology
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cyclooxygenase 2 Inhibitors
  • Protective Agents
  • Celecoxib

Grants and funding

There is no funding source.