s-1743 and Reperfusion-Injury

Proton pump inhibitors (PPIs) are often prescribed in association with clopidogrel and aspirin to patients with myocardial infraction (MI), but their effects on heart is controversial. The purpose of this study was to investigate the effects and potential mechanism of omeprazole (OME) and esomeprazole (ESO) in myocardial ischemia reperfusion (I/R) injury. In the present study, mice were treated with OME, ESO or vehicle for 3 weeks and then subjected to myocardial I/R or sham surgery. At 1 day after surgery, echocardiography was performed to access cardiac injury. Hematoxylin and eosin (H&E) staining was performed to evaluate cardiomyocyte morphology. The IL1β was evaluated by Immunohistochemistry (IHC). Elisa was used to detect cTnt content in serum. The expression of CD86, CD206, CHOP, ATF6, eIF2α and p eIF2α were determined by Western blot (WB). The result showed that ESO markedly improved the left ventricular ejection fraction (LVEF), shortening fraction (FS), suppressed inflammatory infiltration, endoplasmic reticulum stress (ERS) and decreased proinflammatory macrophages in I/R hearts, while OME had no significant effects on cardiac function, inflammation and ERS in the I/R heart. In conclusion, ESO but not OME pretreatment reduces the proportion of proinflammatory macrophages, inhibits endoplasmic reticulum stress, and alleviates I/R injury in mice, indicating that ESO maybe a more proper PPI than OME for application in I/R injury.

Topics: Animals; Apoptosis; Endoplasmic Reticulum Stress; Esomeprazole; Mice; Myocardial Reperfusion Injury; Myocytes, Cardiac; Reperfusion Injury; Stroke Volume; Ventricular Function, Left

The ischemia and subsequent reperfusion (IR) which occurs in partial nephrectomy used in the treatment of renal tumors causes loss of parenchyma in the damaged kidney. The aim of this study is to evaluate, both biochemically and histologically, the efficacy of esomeprazole in an ischemia-reperfusion model in rat kidneys.. The rats were randomized into three groups of seven animals each, referred to as the sham, control, and PPI groups. In the sham group, only a laparotomy was performed. In the control group, following laparotomy the left renal artery was dissected and tied for 30-min ischemia. In the PPI group, a vascular route to the tail vein was opened, and 10 mg/kg esomeprazole was administered. After 1 h, the same procedures described for the control group were performed. All the animals were killed 24 h after the procedure. Biochemical analyses were applied for evaluation of oxidant and antioxidant agents in the blood and left kidney of each subject (oxidative markers: malondialdehyde, myeloperoxidase; antioxidant marker: superoxide dismutase). In the histological examination of the kidney tissues stained with hematoxylin-eosin, the TUNEL method was applied in the evaluation of apoptosis.. No statistically significant biochemical difference was determined in the blood and tissue samples. In the histological and apoptosis evaluations, a statistically significant difference was determined between the sham, control, and PPI groups. The median (IQR) values of the TUNEL-positive cells were counted as 1.50 (4) in the sham group, 11.50 (12) in the control group, and 6.00 (9) in the PPI group (p < 0.001).. A protective effect of esomeprazole was confirmed in renal ischemia-reperfusion damage created in an experimental rat model.

Topics: Animals; Apoptosis; Enzyme Inhibitors; Esomeprazole; Kidney; Kidney Neoplasms; Malondialdehyde; Models, Theoretical; Nephrectomy; Oxidative Stress; Rats; Reperfusion Injury; Superoxide Dismutase; Treatment Outcome