Protective effects of melatonin and glucagon‐like peptide‐1 receptor agonist (liraglutide) on gastric ischaemia–reperfusion injury in high‐fat/sucrose‐fed rats

Abstract

Ischaemia-reperfusion (I-R) injury is a serious pathology that is often encountered with thrombotic events, during surgery when blood vessels are cross-clamped, and in organs for transplantation. Increased oxidative stress is the main pathology in I-R injury, as assessed in studies on the heart, kidney, and brain with little data available on gastric I-R (GI-R). Liraglutide is a GLP-1 receptor agonist that has insulinotropic and weight reducing actions, and melatonin that has been much studied as a chronotropic hormone; have also studied as being anti-oxidative stress agents. Herein, we aimed to explore the effects of liraglutide and melatonin on GI-R injury with high-fat/sucrose diet. Rats were divided into six groups; two diet-control, two melatonin- and two liraglutide-pretreated groups. All rats were subjected to 30 minutes of gastric ischaemia followed by 1 hour of reperfusion. Gastric tissues were assessed for the percentage of DNA fragmentation, myeloperoxidase activity, total oxidant status, total antioxidant capacity, oxidative stress index, BMI and histopathological examination. We showed that high-fat feeding for four weeks prior to GI-R significantly increased BMI, oxidative stress indices and decreased total antioxidant capacity, with a neutral effect on apoptosis compared to controls. Pretreatment with either melatonin (10 mg/kg per day orally) or liraglutide (25 μg/kg per day ip) reverses these effects. Furthermore, both drugs reduced weight only in HFS-fed rats. Both liraglutide and melatonin have nearly similar protective effects on gastric I-R injury through decreasing the oxidative stress and apoptosis.

Melatonin protects the heart and endothelium against high fructose corn syrup consumption–induced cardiovascular toxicity via SIRT-1 signaling

“…As a potent antioxidant, MLT reversed the oxidative parameters of heart in previous studies. 45,46 As expected, MLT treatment ameliorated the oxidative changes in our study, too.…”

Effect of Intravenous Ibuprofen on Ischemia-Reperfusion Injury Following Perioperative Tourniquet in Patients Undergoing Total Knee Arthroplasty

“…This effect was reversed in the other two groups given melatonin and liraglutide. The effect of two drugs in preventing oxidative stress is shown on these parameters [24]. In our study, the fact that TOS was not statistically significant in both groups may indicate that ibuprofen does not contribute to TOS value.…”

Effect of melatonin on electrical impedance and biomarkers of damage in a gastric ischemia/reperfusion model

“…Under reperfusion conditions, epithelial cells can be found in the process of edema. At the level of the lamina propria there is a generation of vascular congestion and zones of hemorrhage (abundant presence of erythrocytes) as well as a presence of inflammatory cells (macrophages, neutrophils) [ 20 , 31 ], these tissue characteristics reduce extracellular space causing the increase of R L , while the increase in X H is related to the loss of membrane integrity and cell death [ 35 ]. After treatment with MT, the decrease in the inflammatory process and cell death, in addition to the presence of granulation tissue are reflected in the measurements of R L and X H , which decrease after the regeneration process.…”

“…The apoptosis assay TUNEL showed a statistically significant increase in the number of cells in the apoptotic process, which is reversed after treatment with MT. Pretreatment with MT has been shown to have a gastroprotective effect of I/R damage by reducing apoptosis [ 20 ]. Similar results have been reported by Wang et al .…”

“…In preclinical studies, it has been shown that both pretreatment (preventive) and treatment (corrective) with MT has gastroprotective effects after inducing acute lesions in the gastric mucosa by I/R. Due to its antioxidant properties, it reduces oxidative stress, increases the activation of antioxidant enzymes and the production of prostaglandins, and decreases neutrophil infiltration and gastric mucosal cell apoptosis [ 18 – 20 ]. However, the effect of treatment with MT on the electrical properties of the gastric mucosa after inducing I/R lesions has not been studied to date.…”