Sepsis, systemic hyper-inflammatory immune response, causes the increase of morbidity and mortality rates due to multi-organ diseases such as neurotoxicity. Lipopolysaccharide (LPS) induces inflammation, oxidative stress and apoptosis to cause brain damage. We aimed to evaluate the antioxidant, anti-inflammatory and antiapoptotic effects of Agomelatine (AGM) on LPS induced brain damage via NF-kB signaling. Twenty-four animals were divided into three groups as control, LPS (5 mg/kg) and LPS + AGM (20 mg/kg). Six hours after the all administrations, rats were sacrificed, brain tissues were collected for biochemical, histopathological and immunohistochemical analysis. In LPS group; total oxidant status (TOS), OSI index, Caspase-8 (Cas-8), NF-kß levels increased and Total antioxidant status (TAS) levels decreased biochemically and Cas-8, haptoglobin and IL-10 expressions increased and sirtuin-1 (SIRT-1) levels decreased immunohistochemically. AGM treatment reversed these parameters except haptoglobin levels in hippocampus and SIRT-1 levels in cerebellum. Besides, AGM treatment blocked the phosphorylation of NF-kB biochemically and ameliorated increased the levels of hyperemia, edema and degenerative changes histopathologically. In conclusion, AGM enhanced SIRT-1 levels to negatively regulate the transcription and activation of p-NF-kB/p65 which caused to ameliorate inflammation, oxidative stress and apoptosis.

中文翻译：

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阿戈美拉汀可预防 LPS 诱导的大鼠神经炎症的脑和小脑损伤

脓毒症是全身性高炎症免疫反应，由于神经毒性等多器官疾病导致发病率和死亡率增加。脂多糖 (LPS) 诱导炎症、氧化应激和细胞凋亡，从而导致脑损伤。我们旨在评估阿戈美拉汀 (AGM) 通过 NF-kB 信号传导对 LPS 诱导的脑损伤的抗氧化、抗炎和抗凋亡作用。将二十四只动物分为三组作为对照，LPS (5 mg/kg) 和 LPS + AGM (20 mg/kg)。全部给药后6小时，处死大鼠，收集脑组织进行生化、组织病理学和免疫组织化学分析。在 LPS 组中；总氧化状态 (TOS)、OSI 指数、Caspase-8 (Cas-8)、NF-kß 水平升高和总抗氧化状态 (TAS) 水平在生化和 Cas-8 上降低，结合珠蛋白和 IL-10 表达增加，而 sirtuin-1 (SIRT-1) 水平在免疫组织化学上降低。AGM 治疗逆转了这些参数，除了海马中的触珠蛋白水平和小脑中的 SIRT-1 水平。此外，AGM 治疗在生化上阻断了 NF-kB 的磷酸化，并在组织病理学上改善了充血、水肿和退行性变化水平的增加。总之，AGM 增强 SIRT-1 水平以负调节 p-NF-kB/p65 的转录和激活，从而改善炎症、氧化应激和细胞凋亡。AGM 治疗在生化上阻断了 NF-kB 的磷酸化，并在组织病理学上改善了充血、水肿和退行性变化水平的增加。总之，AGM 增强 SIRT-1 水平以负调节 p-NF-kB/p65 的转录和激活，从而改善炎症、氧化应激和细胞凋亡。AGM 治疗在生化上阻断了 NF-kB 的磷酸化，并在组织病理学上改善了充血、水肿和退行性变化水平的增加。总之，AGM 增强 SIRT-1 水平以负调节 p-NF-kB/p65 的转录和激活，从而改善炎症、氧化应激和细胞凋亡。