Modulation of Oxidative Stress and Nuclear Factor-κB- Associated Inflammatory Signaling by Rabeprazole in Acetic...

Area of Science:

• Gastroenterology
• Pharmacology
• Cellular Biology

Background:

• Proton pump inhibitors (PPIs) may possess anti-inflammatory and antioxidant properties beyond acid suppression.
• The therapeutic potential of PPIs in inflammatory bowel disease (IBD) requires further investigation.
• Acetic acid-induced colonic injury (AAIC) serves as a relevant model for studying colonic inflammation and oxidative stress.

Purpose of the Study:

• To investigate the effects of rabeprazole on oxidative stress and inflammatory pathways in an AAIC rat model.
• To compare the efficacy of rabeprazole with prednisolone in mitigating colonic injury.
• To evaluate the combined effects of rabeprazole and prednisolone.

Main Methods:

• Forty male Wistar albino rats were divided into five groups: control, AAIC, rabeprazole, prednisolone, and combination therapy.
• Colonic injury was induced via transrectal administration of 3% acetic acid.
• Macroscopic and histopathological assessments were performed, alongside immunohistochemical analysis of 8-hydroxy-2'-deoxyguanosine (8-OHdG), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB).
• Serum levels of malondialdehyde (MDA), glutathione, superoxide dismutase (SOD), and catalase (CAT) were quantified.

Main Results:

• Rabeprazole significantly reduced histopathological damage and inflammatory cell infiltration in the colon.
• Treatment with rabeprazole led to decreased expression of 8-OHdG, TGF-β, TNF-α, and NF-κB.
• Rabeprazole administration resulted in reduced MDA levels and increased SOD and CAT activities, mirroring the effects of prednisolone.
• Combined rabeprazole and prednisolone treatment did not enhance protective responses and showed reduced efficacy compared to monotherapy.

Conclusions:

• Rabeprazole effectively modulates oxidative stress and inflammatory pathways, alleviating colonic tissue injury in an experimental model.
• The anti-inflammatory and antioxidant effects of rabeprazole are comparable to those of prednisolone in this model.
• Combination therapy with rabeprazole and prednisolone does not offer additive benefits and may diminish protective effects, warranting further mechanistic studies.