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Lipopolysaccharide (LPS) is an endotoxin that induces systemic inflammatory responses. Melittin, a main constituent of bee venom, exerts several biological activities such as antioxidant, anti\u2010inflammatory, and antiapoptotic actions. However, whether melittin protects against endotoxin\u2010induced AKI remains undetermined. Here, we aimed to examine the potential action of melittin on LPS\u2010induced renal injury and explore the mechanisms. We showed that acute renal failure and structural damage after injection of LPS were markedly attenuated by administration of melittin. The peptide also suppressed expression of markers of direct tubular damage in kidneys of the LPS\u2010treated mice. Mechanistically, melittin reduced systemic and renal levels of cytokines and inhibited renal accumulation of immune cells with concomitant suppression of nuclear factor kappa\u2010B pathway. Increased amounts of lipid peroxidation products after LPS treatment were largely decreased by melittin. Additionally, the peptide decreased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and enhanced nuclear factor erythroid\u20102\u2010related factor 2\u2010mediated antioxidant defenses. Moreover, melittin inhibited apoptotic and necroptotic cell death after LPS treatment. Lastly, we showed that melittin improved the survival rate of LPS\u2010injected mice. These results suggest that melittin ameliorates endotoxin\u2010induced AKI and mortality through inhibiting inflammation, oxidative injury, and apoptotic and necroptotic death of tubular epithelial cells.<\/jats:p>","DOI":"10.1155\/2021\/8843051","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T18:32:43Z","timestamp":1609871563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Melittin Ameliorates Endotoxin\u2010Induced Acute Kidney Injury by Inhibiting Inflammation, Oxidative Stress, and Cell Death in 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