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

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
• cox-2
• celecoxib

Disclosure Statement

The authors declare that they have no conflict of interest.

Ethics statement

This study was conducted in compliance with Guide for the Care and Use of Laboratory Animals, and all animal experiments were performed under the supervision of Medical Ethics Committee of Laboratory Animals in our hospital.

Author Contributions

Ling Sun conducted the whole study.

Additional information

Funding

There is no funding source.