Department of Immunology, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea.
Department of Internal Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea.
Oxid Med Cell Longev. 2021 Jan 4;2021:8843051. doi: 10.1155/2021/8843051. eCollection 2021.
Sepsis-related acute kidney injury (AKI) is a worldwide health problem, and its pathogenesis involves multiple pathways. 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-inflammatory, and antiapoptotic actions. However, whether melittin protects against endotoxin-induced AKI remains undetermined. Here, we aimed to examine the potential action of melittin on LPS-induced 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-treated mice. Mechanistically, melittin reduced systemic and renal levels of cytokines and inhibited renal accumulation of immune cells with concomitant suppression of nuclear factor kappa-B 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-2-related factor 2-mediated antioxidant defenses. Moreover, melittin inhibited apoptotic and necroptotic cell death after LPS treatment. Lastly, we showed that melittin improved the survival rate of LPS-injected mice. These results suggest that melittin ameliorates endotoxin-induced AKI and mortality through inhibiting inflammation, oxidative injury, and apoptotic and necroptotic death of tubular epithelial cells.
脓毒症相关性急性肾损伤（AKI）是一个全球性的健康问题，其发病机制涉及多个途径。脂多糖（LPS）是一种内毒素，可引起全身炎症反应。蜂毒肽是蜂毒的主要成分之一，具有抗氧化、抗炎和抗凋亡等多种生物学活性。然而，蜂毒肽是否能预防内毒素诱导的 AKI 尚不清楚。在这里，我们旨在研究蜂毒肽对 LPS 诱导的肾损伤的潜在作用，并探讨其机制。我们发现，蜂毒肽给药可明显减轻 LPS 注射后急性肾衰竭和结构损伤。该肽还抑制了 LPS 处理小鼠肾脏中直接肾小管损伤标志物的表达。在机制上，蜂毒肽降低了全身和肾脏细胞因子的水平，并抑制了肾内免疫细胞的积聚，同时抑制了核因子 kappa-B 途径。LPS 处理后脂质过氧化产物的增加在很大程度上被蜂毒肽减少。此外，该肽还降低了烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4 的表达，并增强了核因子红细胞 2 相关因子 2 介导的抗氧化防御。此外，蜂毒肽抑制了 LPS 处理后的细胞凋亡和坏死性细胞死亡。最后，我们发现蜂毒肽提高了 LPS 注射小鼠的存活率。这些结果表明，蜂毒肽通过抑制炎症、氧化损伤以及肾小管上皮细胞的凋亡和坏死性死亡，改善了内毒素诱导的 AKI 和死亡率。
