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. 2023 Nov 9;72(4):505-512.
doi: 10.1538/expanim.23-0052. Epub 2023 Jun 13.

Effect of felodipine on indomethacin-induced gastric ulcers in rats

Nergis Akbaş  1 , Bahadır Süleyman  2 , Renad Mammadov  2 , Mine Gülaboğlu  3 , Emin Murat Akbaş  4 , Halis Süleyman  2
Affiliations

Effect of felodipine on indomethacin-induced gastric ulcers in rats

Nergis Akbaş et al. Exp Anim. .

Abstract

Felodipine is a calcium channel blocker with antioxidant and anti-inflammatory properties. Researchers have stated that oxidative stress and inflammation also play a role in the pathophysiology of gastric ulcers caused by nonsteroidal anti-inflammatory drugs. The aim of this study was to investigate the antiulcer effect of felodipine on indomethacin-induced gastric ulcers in Wistar rats and compare it with that of famotidine. The antiulcer activities of felodipine (5 mg/kg) and famotidine were investigated biochemically and macroscopically in animals treated with felodipine (5 mg/kg) and famotidine in combination with indomethacin. The results were compared with those of the healthy control group and the group administered indomethacin alone. It was observed that felodipine suppressed the indomethacin-induced malondialdehyde increase (P<0.001); reduced the decrease in total glutathione amount (P<0.001), reduced the decrease superoxide dismutase (P<0.001), and catalase activities (P<0.001); and significantly inhibited ulcers (P<0.001) at the tested dose compared with indomethacin alone. Felodipine at a dose of 5 mg/kg reduced the indomethacin-induced decrease in cyclooxygenase-1 activity (P<0.001) but did not cause a significant reduction in the decrease in cyclooxygenase-2 activity. The antiulcer efficacy of felodipine was demonstrated in this experimental model. These data suggest that felodipine may be useful in the treatment of nonsteroidal anti-inflammatory drug-induced gastric injury.

Keywords: felodipine; indomethacin; inflammation; oxidative stress; peptic ulcer.

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Figures

Fig. 1.
Fig. 1.
MDA and GSH levels of the groups. HC: healthy control group; IND: indomethacin group; Fel+IND: felodipine + indomethacin group; Fam+IND: famotidine + indomethacin group; MDA: malondialdehyde; GSH: glutathione. * Statistically significant difference of the groups in comparison to the IND group (P<0.001).
Fig. 2.
Fig. 2.
SOD and CAT levels of the groups. HC: healthy control group; IND: indomethacin group; Fel+IND: felodipine + indomethacin group; Fam+IND: famotidine + indomethacin group; SOD: superoxide dismutase; CAT: catalase. * Statistically significant difference of the groups in comparison to the IND group (P<0.001).
Fig. 3.
Fig. 3.
COX-1 levels of the groups. HC: healthy control group; IND: indomethacin group; Fel+IND: felodipine + indomethacin group; Fam+IND: famotidine + indomethacin group; COX-1: cyclooxygenase-1. * Statistically significant difference of the groups in comparison to the IND group (P<0.001).
Fig. 4.
Fig. 4.
COX-2 levels of the groups. HC: healthy control group; IND: indomethacin group; Fel+IND: felodipine + indomethacin group; Fam+IND: famotidine + indomethacin group; COX-2: cyclooxygenase-2. * Statistically significant difference of the groups in comparison to the IND group (P<0.001).
Fig. 5.
Fig. 5.
Macroscopic photographs of rats’ stomachs. (a) Gastric tissue of the HC group, mucosa with no lesion or redness. (b) Gastric tissue of the IND group, severely hemorrhagic ulcerated mucosa surface. (c) Gastric tissue of the Fel+IND group, minor injuries with normal mucosa. (d) Gastric tissue of the Fam+IND group, minor injuries with normal mucosa. HC: healthy control group; IND: indomethacin group; Fel+IND: felodipine + indomethacin group; Fam+IND: famotidine + indomethacin group.
Fig. 6.
Fig. 6.
Number of ulcers in groups. HC: healthy control group; IND: indomethacin group; Fel+IND: felodipine + indomethacin group; Fam+IND: famotidine + indomethacin group. * Statistically significant difference of the groups in comparison to the IND group (P<0.001).
Fig. 7.
Fig. 7.
Ulcerated areas in groups. HC: healthy control group; IND: indomethacin group; Fel+IND: felodipine + indomethacin group; Fam+IND: famotidine + indomethacin group. *Statistically significant difference of the groups in comparison to the IND group (P<0.001).
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