1 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
2 Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy.
Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419862736. doi: 10.1177/2058738419862736.
Hepatic ischemia/reperfusion injury (IRI) is a clinical condition that may lead to cellular injury and organ dysfunction that can be observed in different conditions, such as trauma, shock, liver resection, and transplantation. Moderate levels of nitric oxide (NO) produced by the endothelial isoform of the NO synthase protect against liver IRI. GIT-27NO is a NO-derivative of the toll-like receptor 4 antagonist VGX-1027 that has been shown to possess both antineoplastic and immunomodulatory properties in vitro and in vivo. In this study, we have investigated the effects of this compound in vitro, in a model of oxidative stress induced in HepG2 cells by hydrogen peroxide (HO), and in vivo, in a rat model of IRI of the liver. GIT-27NO significantly counteracted the toxic effects induced by the HO on the HepG2 cells and in vivo, GIT-27NO reduced the transaminase levels and the histological liver injury by reducing necrotic areas with preservation of viable tissue. These effects were almost similar to that of the positive control drug dimethyl fumarate. These data suggest that the beneficial effect of GIT-27NO in the hepatic IRI can be secondary to anti-oxidative effects and hepatocyte necrosis reduction probably mediated by NO release.
肝缺血/再灌注损伤（IRI）是一种临床病症，可能导致细胞损伤和器官功能障碍，这种情况可见于多种情况，如创伤、休克、肝切除术和移植。由内皮型一氧化氮合酶产生的适度水平的一氧化氮（NO）可防止肝IRI。GIT-27NO 是 Toll 样受体 4 拮抗剂 VGX-1027 的一种 NO 衍生物，已在体外和体内显示出具有抗肿瘤和免疫调节特性。在这项研究中，我们研究了该化合物在体外，通过过氧化氢（HO）诱导 HepG2 细胞发生氧化应激模型中的作用，以及在体内，肝 IRI 的大鼠模型中的作用。GIT-27NO 显著拮抗了 HO 对 HepG2 细胞的毒性作用，并且在体内，GIT-27NO 通过减少坏死区并保留存活组织来降低转氨酶水平和肝组织损伤。这些作用与阳性对照药物富马酸二甲酯几乎相似。这些数据表明，GIT-27NO 在肝 IRI 中的有益作用可能继发于抗氧化作用和肝细胞坏死减少，这可能是通过 NO 释放介导的。
