The effect of nebivolol (NBV), a third-generation selective β1- antagonist, on
indomethacin (IND) - induced gastric ulcer in rats was investigated. Thirty two male
rats were used in this study, divided into four groups as follows: control group, IND
ulcer-induced group, IND + NBV (1mg/kg/day, p.o.) group, and IND + NBV
(5mg/kg/day, p.o.) group. Gastric ulcer was induced by a single injection of IND (30
mg/Kg, i.p.); NBV was administered for seven days prior to ulcer induction. At the
end of the experiment, the stomach of each rat was removed for macroscopic
examination and gastric ulcer scoring. The gastric mucosa was prepared for
quantitative real-time polymerase chain reaction (qRT-PCR) and tissue homogenate
preparation for biochemical study. Then, the remaining part was used for
histopathological and immunohistochemical examination. Results showed that NBV
significantly protected rats from indomethacin-induced gastric ulceration. There is a
significant decreased in the mean ulcer number, score and index along with increased
preventive index. Also, NBV significantly decreased the elevations of nitrite⁄nitrate,
malondialdehyde, tumor necrosis factor-α, and interleukin-1beta in IND-treated rats.
In addition, NBV significantly ameliorated the IND-induced reductions of glutathione
level, glutathione peroxidase, superoxide dismutase, and catalase activities, and
prostaglandin E2. Moreover, histopathological, immunohistochemical analysis of
inducible nitric oxide synthase (iNOS) and qRT-PCR for mRNA expression of iNOS
gene:confirmed the biochemical results. It was concluded that NBV renders protection
in IND-induced gastric ulceration in rats via maintenance of mucosal nitric oxide and
prostaglandin E2, reducing oxidative stress and inflammatory responses |
