alamandine and Acute-Kidney-Injury

Sepsis is defined as the dysregulated immune response leading to multi-organ dysfunction and injury. Sepsis-induced acute kidney injury is a significant contributor to morbidity and mortality. Alamandine (ALA) is a novel endogenous peptide of the renin-angiotensin-aldosterone system. It is known for its anti-inflammatory and anti-apoptotic effects, but its functional and vascular effects on sepsis remain unclear. We aimed to investigate the effects of ALA, as a pre- and post-treatment agent, on lipopolysaccharide (LPS)-induced systemic and renal dysfunction and injury in the LPS-induced endotoxemia model in rats via functional, hemodynamic, vascular, molecular, biochemical, and histopathological evaluation. 10 mg/kg intraperitoneal LPS injection caused both hepatic and renal injury, decreased blood flow in several organs, and renal dysfunction at 20 h in Sprague-Dawley rats. Our results showed that ALA treatment ameliorated systemic and renal inflammation, reduced inflammatory cytokines, prevented the enhancement of the mortality rate, reversed vascular dysfunction, corrected decreased blood flows in several organs, and reduced renal and hepatic injury via inhibiting iNOS (inducible nitric oxide synthase) and caspase expressions in the kidney. In addition, expressions of different ALA-related receptors showed alterations in this model, and ALA treatment reversed these alterations. These data suggest that ALA's systemic and renal protective effects are achieved through its anti-inflammatory, anti-pyroptotic, and anti-apoptotic effects on hemodynamic and vascular functions via reduced iNOS expression.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Kidney; Lipopolysaccharides; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Sepsis

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