alamandine and Reperfusion-Injury

Stroke, a leading cause of mortality and disability, characterized by neuronal death, can be induced by a reduction or interruption of blood flow. In this study, the role of Alamandine, a new peptide of the renin-angiotensin system, was evaluated in in-vitro and in-vivo brain ischemia models.. In the in-vitro model, hippocampal slices from male C57/Bl6 mice were placed in a glucose-free aCSF solution and bubbled with 95% N2 and 5% CO2 to mimic brain ischemia. An Alamandine concentration-response curve was generated to evaluate cell damage, glutamatergic excitotoxicity, and cell death. In the in-vivo model, cerebral ischemia/ reperfusion was induced by bilateral occlusion of common carotid arteries (BCCAo-untreated) in SD rats. An intracerebroventricular injection of Alamandine was given 20-30 min before BCCAo. Animals were subjected to neurological tests 24 h and 72 h after BCCAo. Cytokine levels, oxidative stress markers, and immunofluorescence were assessed in the brain 72 h after BCCAo.. Alamandine was able to protect brain slices from cellular damage, excitotoxicity and cell death. When the Alamandine receptor was blocked, protective effects were lost. ICV injection of Alamandine attenuated neurological deficits of animals subjected to BCCAo and reduced the number of apoptotic neurons/cells. Furthermore, Alamandine induced anti-inflammatory effects in BCCAo animals as shown by reductions in TNFα, IL- 1β, IL-6, and antioxidant effects through attenuation of the decreased SOD, catalase, and GSH activities in the brain.. This study showed, for the first time, a neuroprotective role for Alamandine in different ischemic stroke models.

Topics: Animals; Brain Ischemia; Disease Models, Animal; Humans; Ischemic Stroke; Male; Mice; Neuroprotection; Neuroprotective Agents; Oligopeptides; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stroke

This study was to determine whether alamandine (Ala) could reduce ischaemia and reperfusion (I/R) injury of kidney in rats.. Renal I/R was induced by an occlusion of bilateral renal arteries for 70 min and a 24-h reperfusion in vivo, and rat kidney proximal tubular epithelial cells NRK52E were exposed to 24 h of hypoxia and followed by 3-h reoxygenation (H/R) in vitro.. The elevated serum creatinine (Cr), blood cystatin C (CysC) and blood urea nitrogen (BUN) levels in I/R rats were inhibited by Ala treatment. Tumour necrosis factor alpha (TNF)-α, IL-1β, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax were increased, and Bcl2 was reduced in the kidney of I/R rats, which were reversed by Ala administration. Ala reversed the increase of TNF-α, IL-1β, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax and the decrease of Bcl2 in the H/R NRK52E cells. Ala could also inhibit the increase of oxidative stress levels in the kidney of I/R rats. NADPH oxidase 1 (Nox1) overexpression reversed the improving effects of Ala on renal function, inflammation and apoptosis of I/R rats.. These results indicated that Ala could improve renal function, attenuate inflammation and apoptosis in the kidney of I/R rats via inhibiting oxidative stress.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Caspase 8; Cell Line; Disease Models, Animal; Inflammation; Interleukin-1beta; Interleukin-6; Ischemia; Kidney; Kidney Tubules, Proximal; Male; NADPH Oxidase 1; Oligopeptides; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha