Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska Str. 64/13, Kiev, 01601, Ukraine.
Department of Biotechnical Problems in Diagnostic, Institute for Problems of Cryobiology and Cryomedicine, Nauki Ave. 42/1, Kiev, 03028, Ukraine.
Dig Dis Sci. 2020 Jan;65(1):215-224. doi: 10.1007/s10620-019-05730-3. Epub 2019 Jul 16.
A significant role in pathogenesis of cholangitis is attributed to excessive reactive oxygen species production and oxidative stress. Therefore, antioxidants could be promising therapeutics.
The effects of powerful free radical scavenger C fullerene on hepatic and pancreatic manifestations of acute and chronic cholangitis in rats were aimed to be discovered.
Acute (AC, 3 days) and chronic (CC, 28 days) cholangitis models were simulated by single (AC) and 4 weekly (CC) α-naphthylisothiocyanate per os administrations. Pristine C fullerene aqueous colloid solution (CFAS, 0.15 mg/ml, size of aggregates 1.2-100 nm) was administered either per os or intraperitoneally at a dose of 0.5 mg/kg C fullerene daily (AC) and every other day (CC). Prednisolone was used as a reference. Liver and pancreas autopsies were analyzed, and blood serum biochemical markers were measured. Pan-cytokeratin expression in HepG2 cells was assessed after 48-h incubation with CFAS.
On AC, CFAS normalized elevated bilirubin, alkaline phosphatase, and triglycerides, diminished fibrotic alterations in liver, and improved pancreas state when applied by both ways. Additionally, CFAS per os significantly reduced the signs of inflammation in liver and pancreas. On CC, CFAS also mitigated liver fibrosis and inflammation, improved pancreas state, and normalized alkaline phosphatase and triglycerides. The remedy effect of CFAS was more expressed compared to that of prednisolone on both models. Furthermore, CFAS inhibited pan-cytokeratin expression in HepG2 cells in a dose-dependent manner.
Pristine C fullerene inhibits liver inflammation and fibrogenesis and partially improved liver and pancreas state under acute and chronic cholangitis.
过量的活性氧(ROS)产生和氧化应激被认为在胆管炎的发病机制中起着重要作用。因此,抗氧化剂可能是有前途的治疗方法。
旨在发现强大的自由基清除剂 C 富勒烯对大鼠急性和慢性胆管炎的肝和胰腺表现的影响。
通过单次(AC)和 4 周(CC)α-萘基异硫氰酸酯口服给药模拟急性(AC)和慢性(CC)胆管炎模型。将原始 C 富勒烯水胶体溶液(CFAS,0.15mg/ml,聚集物尺寸为 1.2-100nm)经口或腹膜内给药,剂量为 0.5mg/kg C 富勒烯,每日(AC)或隔日(CC)一次。泼尼松龙作为参考。分析肝和胰腺尸检,并测量血清生化标志物。用 CFAS 孵育 HepG2 细胞 48 小时后,评估泛细胞角蛋白的表达。
在 AC 时,CFAS 使升高的胆红素、碱性磷酸酶和甘油三酯正常化,减少肝纤维化改变,并改善胰腺状态,两种途径均有应用。此外,CFAS 经口还显著减轻肝和胰腺的炎症迹象。在 CC 时,CFAS 还减轻肝纤维化和炎症,改善胰腺状态,并使碱性磷酸酶和甘油三酯正常化。与泼尼松龙相比,CFAS 在两种模型中的疗效更为显著。此外,CFAS 以剂量依赖的方式抑制 HepG2 细胞中泛细胞角蛋白的表达。
原始 C 富勒烯可抑制急性和慢性胆管炎时的肝炎症和纤维化,并部分改善肝和胰腺状态。