Department of Biochemistry, Faculty of Pharmacy, Atatürk University, Erzurum, 25240, Turkey.
Department of Biochemistry, Faculty of Medicine, Atatürk University, Erzurum, 25240, Turkey.
Biomed Pharmacother. 2020 Jul;127:110206. doi: 10.1016/j.biopha.2020.110206. Epub 2020 May 4.
Sepsis is a pathophysiological event involving systemic inflammatory response syndrome, multiple organ failure syndromes, and tissue damage. Overproduction of free radicals as a result of tissue damage during sepsis contributes to cellular toxicity, organ failure, and even mortality. Antioxidants, which scavenge free radicals, play a protective role against various diseases. Previous studies have shown that umbelliferone (UF) has antioxidant and anti-inflammatory effects. Since oxidative stress is naturally associated with sepsis-induced organ dysfunction, the application of antioxidant compounds could potentially illuminate the pathophysiology of sepsis, which does not yet have an effective treatment. The sepsis model induced by cecal ligation and puncture (CLP) was applied to rats. Different doses of UF (10░mg/kg, 20░mg/kg, and 40░mg/kg) on oxidant-antioxidant in septic rats, mRNA of inflammatory mediators such as tumor necrosis factor- α (TNF-α) and interleukin (IL)-1 its effects on expression levels were evaluated in lung, kidney, and liver tissues. When the lung, kidney, and liver tissues of septic rats were compared with those of the control group, it was found that UF administration increased dose-dependent superoxide dismutase activity and glutathione levels and significantly decreased malondialdehyde levels. The effects of UF administration on oxidative parameters were dose-dependent. The 40░mg/kg UF dose showed greater anti-oxidative properties than the 20░mg/kg and 10░mg/kg doses for all the evaluated parameters. Further, the TNF- α mRNA expression of the CLP +40░mg/kg group was reduced to a level comparable to that of the control group. UF has been found to be an effective molecule in reducing oxidative stress by supporting endogenous antioxidants and enhancing the scavenging effects of free radicals. The potent antioxidant property of UF may also be related to the suppression of the cytokine cascade during sepsis. The results suggest that UF administration may represent a new treatment for the prevention of lung, kidney and liver damage caused by septic conditions.
脓毒症是一种涉及全身炎症反应综合征、多器官衰竭综合征和组织损伤的病理生理事件。脓毒症时组织损伤导致自由基的过度产生导致细胞毒性、器官衰竭甚至死亡。清除自由基的抗氧化剂在各种疾病中发挥保护作用。先前的研究表明，蛇床子素（UF）具有抗氧化和抗炎作用。由于氧化应激与脓毒症引起的器官功能障碍自然相关，因此应用抗氧化化合物可能阐明目前尚无有效治疗方法的脓毒症的病理生理学。将盲肠结扎和穿刺（CLP）诱导的脓毒症模型应用于大鼠。在脓毒症大鼠中评估不同剂量 UF（10mg/kg、20mg/kg 和 40mg/kg）对氧化剂-抗氧化剂的作用，以及在肺、肾和肝组织中炎症介质如肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-1 的 mRNA 表达水平。与对照组相比，脓毒症大鼠的肺、肾和肝组织中发现，UF 给药剂量依赖性地增加超氧化物歧化酶活性和谷胱甘肽水平，并显著降低丙二醛水平。UF 给药对氧化参数的影响呈剂量依赖性。与 20mg/kg 和 10mg/kg 剂量相比，40mg/kg UF 剂量对所有评估参数显示出更大的抗氧化特性。此外，CLP+40mg/kg 组的 TNF-α mRNA 表达降低到与对照组相当的水平。UF 已被发现是一种通过支持内源性抗氧化剂和增强自由基清除作用来减少氧化应激的有效分子。UF 的强大抗氧化特性也可能与脓毒症期间细胞因子级联的抑制有关。这些结果表明，UF 给药可能代表一种预防脓毒症引起的肺、肾和肝损伤的新治疗方法。
