title: [Effect of ozonized saline on signaling passway of Keap1-Nrf2-ARE in rat hepatocytes].
abstract: OBJECTIVE
  To study the effect of ozonized saline on the activation of the Keap1-Nrf2-ARE signaling pathway in rat liver cells.
  
  
  METHODS
  Twenty male Sprague-Dawley rats were randomly divided into ozonized saline (OS) group, model group, ozonized saline control (OSC) group and normal control (NC) group. The rats in OS group and model group were intravenously administered with OS or oxygen saline (5 ml/kg) respectively, once a day for 15 days, and then intraperitoneally injected with CCl4 dissolved in oliver oil. The rats in OSC group were pretreated with OS for 15 days. The rats in NC group were fed normally for 15 days. On the 16th day, the rats in OSC group and NC group were intraperitoneally injected with oliver oil (2 ml/kg) without CCl4. After 24 hours of CCl4 or olive oil intraperitoneal injection, the serum levels of alanine transaminase (ALT) and aspertate aminotransferase (AST) were measured. The liver tissues were also collected for detection of total anti-oxygen capability (TAOC), glutathione (GSH), catalase (CAT), Glutathione peroxidase (GPx). Western Blot was used to detect Nrf2 and immunofluorescence staining assay to display intracelluar distribution of Nrf2.
  
  
  RESULTS
  Compared with the rats in model group,the serum ALT and AST levels of rats in OS group were significantly lower (P < 0.01) ,which were (1240.4 ± 188.2) U/L and (1245.4 ± 176.9) U/L vs (539.8 ± 175.3) U/L and (546.0 ± 130.2) U/L, and the TAOC, CAT, GPx and GSH activity of rats in OS group were significantly higher, which were (0.72 ± 0.24) U/mg, (1.05 ± 0.21) mg/g, (676.9 ± 115.1) U/mg and (45.2 ± 14.3) U/mg vs (1.37 ± 0.19) U/mg, (2.23 ± 0.55) mg/g, (1024.6 ± 162.9) U/mg and (68.2 ± 9.9) U/mg, respectively. In contrast with NC group, pretreatment of OS in OSC group elevated TAOC, CAT, GPx and GSH activity (P < 0.01 or P < 0.05). Ozonized saline can strengthen the Nrf2 expression in liver cells.
  
  
  CONCLUSIONS
  Preconditioning injection of ozonized saline can reduce rat's liver injury induced by CCl4. The ozonized saline, as a novel Nrf2 activator, can reduce the oxidative damage of radical oxygen species (ROS) and the deleterious substance by activating the Keap1-Nrf2-ARE signaling pathway and its downstream genes expression.
authors.affiliation: Department of Infectious Diseases, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Qu
authors.forename: Fu-jiang
authors.initials: FJ
authors.lastname: Peng
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Shu-ling
authors.initials: SL
authors.lastname: Yang
authors.forename: Ya-bing
authors.initials: YB
authors.lastname: Guo
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D000072019:Kelch-Like ECH-Associated Protein 1; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D010126:Ozone / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D011506:Proteins; D008315:Malondialdehyde; D010126:Ozone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D005978:Glutathione