Rivastigmine ameliorates indomethacin experimentally induced gastric mucosal injury via activating α7nAChR with inhibiting oxidative stress and apoptosis

• Published in: Journal of biochemical and molecular toxicology Vol. 36; no. 10; pp. e23147 - n/a
• Main Authors: Khalaf, Hanaa M., Ahmed, Sabreen M., Welson, Nermeen N., Abdelzaher, Walaa Yehia
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2022
• Subjects: Acidity; Antigens; Apoptosis; Caspase; Cholinergics; gastric injury; Gastric juice; Gastric mucosa; Glutathione; Indomethacin; Injuries; Interleukin 6; Interleukins; Mucin; Oxidative stress; Pepsin; Proliferating cell nuclear antigen; Rivastigmine; Superoxide dismutase; Tumor necrosis factor; Tumor necrosis factor-TNF; Ulcers; α7nAChR; gastric injury; rivastigmine; α7nAChR; indomethacin
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.23147

The current study aimed to investigate the potential ameliorative role of Rivastigmine (RIVA), the anti‐Alzheimer drug, against the gastric mucosal injury caused by indomethacin (IND). The rats were divided into four groups: group I was given a vehicle as a control, group II was given RIVA (0.3 mg/kg) once daily intraperitoneal (ip) for 2 weeks, group III was given a single IP dose of 30 mg/kg IND, and group IV was given RIVA ip 2 weeks before the administration of IND. The gastric mucosal injury was detected by the estimation of ulcer index, gastric acidity, pepsin, and mucin concentrations. Malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), total nitrite/nitrate (NOx), and the expression of tumor necrosis factor‐α (TNF‐α), interleukin 6 (IL‐6), nuclear factor kappa B (NF‐κB), Hemoxygenase 1 (HO‐1), and caspase‐3 were all measured in gastric tissue. In addition, histological assessment and proliferating cell nuclear antigen (PCNA) immuno‐expression were studied. Gastric mucosal injury induced by IND was indicated by both biochemical and histopathological assessments. RIVA Pretreatment reduced ulcer index, MDA, TNF‐α, IL‐6, NF‐κB, and caspase‐3 and increased SOD, GSH, NOx, and HO‐1. RIVA improved the suppressed nuclear immunoreaction for PCNA observed with IND. The current findings provide novel evidence that RIVA possesses a prophylactic action against IND‐induced gastric mucosal damage in rats. Despite being a cholinergic drug that is associated with increased pepsin and stomach acidity, RIVA protected against IND‐induced gastric mucosal injury via activating α7nAChR and inhibiting oxidative stress and apoptosis.