Acetaminophen (APAP) is a widely used analgesic and antipyretic agent. APAP is metabolized by a cytochrome P450 system to N-acetyl-p-benzoquinoneimine (NAPQI). Overdose of APAP causes a highly reactive metabolite that depletes the intracellular pool of glutathione (GSH), 1) for NAPQI reacts rapidly with GSH. The abrupt decrease in liver GSH is particularly harmful because it is a basic cytosolic oxidant scavenger and redox regulation capacity, 2) which would exacerbate oxidation stress in conjunction with mitochondrial dysfunction, especially lead to massive hepatocyte necrosis, liver damage or death. Much evidence has pointed to the importance of GSH defense mechanism against the hepatic damage induced by free radicals in many pathophysiological situations involving lipid peroxidation reaction. 3)Oxidative damage, mediated by reactive oxygen species (ROS) which can be generated following cell lysis, oxidative burst, or the presence of an excess of free transition metals, can attack proteins, deoxynucleic acid, and lipid membranes, thereby disrupting cellular function and integrity. 4,5) Malondialdehyde (MDA) is a secondary product of oxidative stress formed during lipid peroxidation processes. Increase in the production of ROS during APAP metabolism leads to increase tumor necrosis factor-alpha (TNF-a) production.6,7) In many forms of liver injury, including ischemia/reperfusion and fulminant hepatic failure, TNF-a signaling appears to play an important role. 8) In the APAP-induced liver damage, TNF-a also participates in the processes causing liver failure, because the administration of anti-TNF-a antibody to APAP-treated animals ameliorated the enzyme leakage during the early phase of the intoxication. 6) Executioner caspases proteolytically cleave a number of cytoskeletal and nuclear structural proteins. This effect is responsible for the characteristic morphological changes of cells undergoing apoptosis such as cell shrinkage, membrane blebbing and chromatin condensation.9) Because of the number of parameters that affect hypoxia inducible factor (HIF) induction and the many downstream targets of this signal transduction factor, HIF is considered to be a generalized stress response gene regulator. In addition to hypoxia, oxidative stress may promote HIF-1a induction. In the following study, we examined the induction of MDA, TNF-a, caspase-3 and HIF-1a in the livers of APAP-induced mice.Salidroside, (SDS, (4-hydroxy-phenethyl)-b-D-glucopyranoside, C 14 H 20 O 7 : 300.30) isolated from Rhodiola sachalinensis A. BOR. (Gao-shan-hong-jing-tian in Chinese) is one of the most popular traditional Chinese medicines.10) Rhodiola sachalinensis has a reputation for stimulating the nervous system, decreasing depression, enhancing work performance, resisting anoxia, preventing high altitude sickness, and is especially famous in the treatment of mountain malhypoxia in China. Rhodiola sachalinensis A. BOR. showed effectively protected against carbon tetrachloride-induced liver injury, resulting in reduced lipid peroxidation...

AIM:To investigate the therapeutic effect of tetrandrine on liver fibrosis induced by thioacetamide in rats in vivo and in vitro . METHODS:In vitro study: we investigated the effect of tetrandrine on the apoptosis of rat hepatic stellate cells transformed by simian virus 40 (T-HSC/Cl-6), which retains the features of activated cells. In vivo study: hepatic fibrosis was induced in rats by thioacetamide. Tetrandrine was given orally to rats at doses of 5, 10 or 20 mg/kg for 4 wk compared with intraperitoneal injection of interferon-г.

Overexpression of Axl has been noted to correlate with several human cancers. However, the regulatory mechanisms and effects of Axl in human neuroblastoma development remain unclear. Here, we explore the expression of Axl in neurobalstoma and related upstream regulatory mechanisms of invasion and migration. We found that Axl was overexpressed in metastatic neuroblastoma tissues and positively associated with long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1. Meanwhile, our data suggested that metastasis-associated lung adenocarcinoma transcript 1 upregulated Axl expression in neuroblastoma cells, resulting in cell invasion and migration. Furthermore, we found that targeting Axl by inhibitor R428 significantly suppressed the abilities of tumor cell invasion and migration. In summary, these results suggested that Axl, which is regulated by long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1, may exert great influence on invasion and migration of neuroblastoma.

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