The effect of liraglutide, a GLP-1 analog, on indomethacin-induced gastric ulcers in diabetic ratsPurpose: To investigate the potential pleiotropic effects of liraglutide (LG), a glucagon-like-peptide-1 analog, on gastric ulcer prevention in rats with diabetes induced by streptozotocin (STZ).
Methods: We randomly divided 63 male Wistar rats into seven groups. STZ was administered intraperitoneally (IP) to the animals in the diabetic control (group STZ), diabetic control + indomethacin (INDO) (group STZI), STZ + INDO + omeprazole (group OMP), STZ + INDO + LG (0.2 mg/kg) (group 0.2LG), and STZ + INDO + LG (0.4 mg/kg) group (group 0.4LG). We administered OMP IP to group OMP, 0.2 mg/kg LG to group 0.2LG SC, 0.4 mg/kg LG to group 0.4LG SC, normal saline to non-diabetic control (sham group), group STZ, non-diabetic control + INDO (group KI), and group STZI SC. INDO was administered to the animals in groups KI, STZI, OMP, 0.2LG, and 0.4LG by gavage. Then, the caspase-3, epidermal growth factor (EGF), vascular endothelial growth factor-A (VEGF-A), prostaglandin E2 (PGE2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), superoxide dismutase-1 (SOD-1), glutathione (GSH), and malondialdehyde (MDA) levels were studied.
Results: LG prevented INDO-induced ulcers and decreased apoptosis in the stomach tissue. It increased the SOD-1, GSH, EGF, VEGF-A, and PGE2 levels, and reduced the MDA, IL-6, and TNF-α levels. The anti-ulcer effect of LG was lower, but close to that of OMP.
Conclusion: The antioxidant, anti-inflammatory, and anti-apoptotic effects of LG, its ability to regulate EGF, VEGF-A, and PGE2 levels, and its capacity to reduce blood glucose levels in diabetic rats may contribute to its anti-ulcer effect.
Key words
Stomach Ulcer; Indomethacin; Liraglutide; Glucagon-Like Peptide 1; Rats
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STZ: streptozotocin; OMP: omeprazole; LG: liraglutide; INDO: indomethacin. Source: Elaborated by the authors.
STZ: streptozotocin. Source: Elaborated by the authors.
STZ: streptozotocin; KI: non-diabetic control + indomethacin; STZI: streptozotocin + indomethacin; OMP: omeprazole; LG: liraglutide (0.2 and 0.4 mg/kg); **p < 0.01; ***p < 0.001 (versus sham and STZ control diabetic); λp < 0.001 (versus all groups); #p < 0.05 (versus STZI). Source: Elaborated by the authors.
STZ: streptozotocin. Source: Elaborated by the authors.
STZ: streptozotocin; KI: non-diabetic control + indomethacin; STZI: streptozotocin + indomethacin; OMP: omeprazole; LG: liraglutide (0.2 and 0.4 mg/kg); **p < 0.01; ***p < 0.001 (versus sham and STZ control diabetic); λp < 0.001 (versus all groups); ###p < 0.001 (versus STZI). Source: Elaborated by the authors.
STZ: streptozotocin. Source: Elaborated by the authors.
STZ: streptozotocin; KI: non-diabetic control + indomethacin; STZI: streptozotocin + indomethacin; OMP: omeprazole; LG: liraglutide (0.2 and 0.4 mg/kg); EGF: epidermal growth factor; VEGF-A: vascular endothelial growth factor-A; PGE2: prostaglandin E2; *p < 0.05, **p < 0.01 and ***p < 0.001 (versus sham); #p < 0.05, ##p < 0.01 and ###p < 0.001 (versus STZI); ^^p < 0.01 (versus 0.2 LG); λp < 0.001 (versus all groups). Source: Elaborated by the authors.
STZ: streptozotocin; KI: non-diabetic control + indomethacin; STZI: streptozotocin + indomethacin; OMP: omeprazole; LG: liraglutide (0.2 and 0.4 mg/kg); IL-6: interleukin-6; TNF: tumor necrosis factor; *p < 0.05, **p < 0.01 and ***p < 0.001 (versus sham); #p < 0.05 (versus STZI); ##p < 0.01 and ###p < 0.001 (versus KI); ^^p < 0.01 (versus 0.2 LG); λp < 0.001 (versus all groups). Source: Elaborated by the authors.
STZ: streptozotocin; KI: non-diabetic control + indomethacin; STZI: streptozotocin + indomethacin; OMP: omeprazole; LG: liraglutide (0.2 and 0.4 mg/kg); SOD-1: superoxide dismutase 1; GSH: glutathione; MDA: malondialdehyde; *p < 0.05, **p < 0.01 and ***p < 0.001 (versus sham and STZ); #p < 0.05 (versus STZI); ##p < 0.01 and ###p < 0.001 (versus STZI); ^^p < 0.01 (versus 0.2 LG); λp < 0.001 (versus all groups). Source: Elaborated by the authors.