Department of Pharmacology, National Organization for Drug Control and Research, Cairo, Egypt.
J Biochem Mol Toxicol. 2018 Aug;32(8):e22175. doi: 10.1002/jbt.22175. Epub 2018 Jul 3.
Renal injury is a hallmark adverse reaction to sodium valproate (SVP), and caffeic acid (CAFF) is a phenolic compound that has anti-inflammatory and antioxsidant properties. So, this investigation was assessed to evaluate the nephrotoxic potential of SVP and the defensive impact of CAFF against SVP nephrotoxicity. SVP was given at a dose of 500 mg/kg (i.p.) once daily for 2 weeks, while CAFF was given at a dose of 50 mg/kg (orally), simultaneously with SVP. Concurrent treatment with CAFF reduced urea and creatinine, lipid peroxidation (malondialdehyde), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), nuclear factor kappa B (NF-κB/p65), and transforming growth factor β (TGF-β) levels. However, with increased glutathione content, CAFF also halted the activated Notch signaling cascade. Furthermore, CAFF suppressed caspase-3 and inducible nitric oxide synthase expressions. To conclude, on the basis of the results obtained, CAFF proved to protect against SVP-induced nephrotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic properties.
肾损伤是丙戊酸钠(SVP)的标志性不良反应,咖啡酸(CAFF)是一种具有抗炎和抗氧化特性的酚类化合物。因此,本研究评估了 SVP 的肾毒性潜力以及 CAFF 对 SVP 肾毒性的防御作用。SVP 以 500mg/kg(ip)的剂量每天一次给予 2 周,而 CAFF 以 50mg/kg(口服)的剂量与 SVP 同时给予。与 CAFF 同时治疗可降低尿素和肌酐、脂质过氧化(丙二醛)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、核因子-κB(NF-κB/p65)和转化生长因子-β(TGF-β)的水平。然而,随着谷胱甘肽含量的增加,CAFF 还阻止了激活的 Notch 信号级联反应。此外,CAFF 抑制了 caspase-3 和诱导型一氧化氮合酶的表达。总之,根据获得的结果,CAFF 通过其抗氧化、抗炎和抗细胞凋亡特性被证明可以预防 SVP 诱导的肾毒性。