Pharmacology and Toxicology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500 007, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 201 002, India.
Pharmacology and Toxicology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500 007, India.
Biomed Pharmacother. 2018 Apr;100:304-315. doi: 10.1016/j.biopha.2018.01.169. Epub 2018 Feb 16.
Sepsis-induced acute kidney injury (AKI) is responsible for 70-80% mortality in intensive care patients due to elevated levels of endotoxin, Lipopolysaccharide (LPS) caused by gram-negative infections. Ferulic acid (FA), a phenolic phytochemical is known for its renal protection on various induced models of nephrotoxicity. However, the curative effect of FA in LPS-induced AKI is not well studied. This study aimed to investigate the effect of FA on LPS-induced AKI in mice model and to understand the protective mechanisms involved, to provide evidence for FA in the treatment of AKI. Balb/c mice were treated with FA at 50 mg/kg and 100 mg/kg dosages after LPS stimulation (10 mg/kg). At the end of the intervention, we determined the concentrations of serum creatinine and blood urea nitrogen, inflammatory cytokines and histopathological changes in animals. Also, the relative protein expression level of TLR4 mediated NF-κB signaling pathway were studied in kidney tissues. FA treated animals showed upregulation of antioxidant defenses and suppression of inflammatory events by inhibiting TLR-4 mediated NFκB activation. However, LPS alone administered group, resulted in rapid renal damage with increased levels of blood urea nitrogen and modest increase in creatinine; decreased antioxidant defenses and release of inflammatory cytokines. The histopathological analysis also revealed the protective action of the FA against sepsis induced fibrosis and renal damage. Our findings demonstrated that FA exhibits marked protective effects on LPS-induced AKI in mice suggesting its chemopotential role for treating AKI in humans.
脓毒症引起的急性肾损伤（AKI）是重症监护患者 70-80%死亡率的原因，这是由于内毒素、脂多糖（LPS）水平升高所致，而革兰氏阴性感染会导致内毒素和 LPS 水平升高。阿魏酸（FA）是一种酚类植物化学物质，已知对各种肾毒性诱导模型具有肾脏保护作用。然而，FA 在 LPS 诱导的 AKI 中的疗效尚未得到充分研究。本研究旨在探讨 FA 对 LPS 诱导的 AKI 小鼠模型的影响，并了解所涉及的保护机制，为 FA 在 AKI 治疗中的应用提供依据。在 LPS 刺激后（10mg/kg），Balb/c 小鼠用 FA 以 50mg/kg 和 100mg/kg 的剂量进行治疗。干预结束时，我们测定了血清肌酐和血尿素氮、炎性细胞因子和动物组织学变化的浓度。此外，还研究了肾脏组织中 TLR4 介导的 NF-κB 信号通路的相对蛋白表达水平。FA 处理的动物表现出抗氧化防御的上调和 TLR-4 介导的 NFκB 激活的抑制，从而抑制炎症事件。然而，单独给予 LPS 的组导致肾功能迅速受损，血尿素氮水平升高，肌酐略有升高；抗氧化防御降低，炎性细胞因子释放。组织病理学分析还揭示了 FA 对脓毒症诱导的纤维化和肾损伤的保护作用。我们的研究结果表明，FA 对 LPS 诱导的 AKI 小鼠具有显著的保护作用，提示其在治疗人类 AKI 方面具有化学治疗潜力。
