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

Proton pump inhibitors have been reported to exert anti-inflammatory and antioxidant effects independent of gastric acid suppression; however, their role in inflammatory bowel disease remains unclear. The current study investigated whether rabeprazole modulates oxidative stress-related and inflammatory pathways in an acetic acid-induced colonic injury (AAIC) and compared these effects with those of prednisolone.

Forty male Wistar albino rats were randomly assigned to 5 groups (n = 8) using a computer-generated sequence. To ensure unbiased results, the control and AAIC groups received sham gavage of 1 mL of 0.9% NaCl on the same schedule as the treatment groups. Colonic injury was induced by transrectal administration of 3% acetic acid. Rabeprazole (20 mg/kg/day) and/ or prednisolone (2 mg/kg/day) were administered orally for 10 days. Macroscopic and histopathological evaluations were performed. Immunohistochemical expression 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) was assessed. Serum malondialdehyde (MDA), glutathione, superoxide dismutase (SOD), and catalase (CAT) levels were measured.

Rabeprazole significantly attenuated histopathological damage and inflammatory cell infiltration compared with the AAIC group. Expression of 8-OHdG, TGF-β, TNF-α, and NF-κB was reduced, accompanied by decreased MDA levels and increased SOD and CAT activities. These effects overlapped with those of prednisolone. Combined administration did not provide additional benefit and was associated with reduced protective responses compared with either agent alone.

Rabeprazole modulates oxidative stress and inflammatory pathways and alleviates tissue injury in experimental colonic injury; however, its effects are not additive with those of prednisolone. Further studies are warranted to clarify the underlying mechanisms.