Melatonin (MT) is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that MT exerts protective effects in septic shock, hemorrhagic shock and inflammation. Lipopolysaccharide (LPS), from Escherichia coli, administered to animals directly stimulates a number of cells and systems to produce various inflammatory mediators. LPS-induced septic shock is characterized by hypotension and vascular hyporeactivity to contracting agents. In particular, the reactive oxygen species such as superoxide and nitric oxide (NO) contribute to the pathophysiology of septic shock. In this study, we demonstrate that MT pretreatment prevents the hyporeactivity to phenylephrine in vivo and in aorta rings collected from rats treated with the endotoxin. The beneficial effect of MT seems related to its antioxidant properties and with inhibition of inducible nitric oxide synthase (iNOS) protein expression, reduction of NO production and nitrotyrosine formation, in aorta, preventing vascular, and endothelial injury. Additionally, we first demonstrate, that MT inhibited nuclear enzyme poly (ADP-ribose) synthetase activation in vascular tissue. The current study underlined the protective effect of MT on the vascular dysfunction associated with septic shock, data that could support the clinical use of MT in human endotoxemia.

中文翻译：

---

褪黑素可预防脂多糖诱导的大鼠反应性降低。

褪黑激素（MT）是松果体的主要分泌产物，其作为免疫调节剂的作用已得到充分确立。最近的证据表明MT对败血性休克，出血性休克和炎症具有保护作用。给予动物的大肠杆菌脂多糖（LPS）可直接刺激许多细胞和系统，产生各种炎症介质。LPS引起的败血性休克的特征在于低血压和血管对收缩剂的反应性低下。特别地，诸如超氧化物和一氧化氮（NO）的活性氧物质有助于败血性休克的病理生理。在这项研究中，我们证明MT预处理可预防体内和在从内毒素治疗的大鼠收集的主动脉环中对去氧肾上腺素的反应性降低。MT的有益作用似乎与其抗氧化性能有关，与抑制主动脉中一氧化氮合酶（iNOS）蛋白表达，减少NO生成和亚硝基酪氨酸形成有关，可预防血管和内皮损伤。此外，我们首先证明MT抑制了血管组织中核酶聚（ADP-核糖）合成酶的活化。当前的研究强调了MT对败血性休克相关血管功能障碍的保护作用，这些数据可以支持MT在人类内毒素血症中的临床应用。MT抑制了血管组织中核酶聚（ADP-核糖）合成酶的活化。当前的研究强调了MT对败血性休克相关血管功能障碍的保护作用，这些数据可以支持MT在人类内毒素血症中的临床应用。MT抑制了血管组织中核酶聚（ADP-核糖）合成酶的活化。当前的研究强调了MT对败血性休克相关血管功能障碍的保护作用，这些数据可以支持MT在人类内毒素血症中的临床应用。