title: New pathways driving the experimental hepatoprotective action of tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) against acute hepatotoxicity.
abstract: OBJECTIVE
  In absence of liver protective drugs, a large number of hepatopathies may arise during drug administration. This study was executed to investigate the possible new pathways underlying the hepatoprotective effect of Tempol (4-hydroxy-2,2,6,6- tetramethylpiperidine-1-oxyl), following oral administration of carbon tetrachloride in mice.
  
  
  RESULTS
  Thirty albino mice were randomized into 3 equal groups. The duration of study was 28 days. The groups were classified as follows: Group I (healthy control): received saline, in the same volume of CCl4 dose, daily, orally, for 14 days, then sacrificed. Group II: received CCl4, as a single oral dose only, of 1 ml/kg body weight, dissolved in olive oil (1:1 v/v), the animals of this group were sacrificed 14 days after CCl4 single dose intoxication. Group III (protective Tempol treated): received a single dose of Tempol, 20mg/kg, orally, daily for 14 days. Two hours after the last Tempol dose, animals of group III received a single oral dose of CCl4. Fourteen days later, animals were scarified to collect blood and liver tissues for analysis. Tempol pretreatment significantly captured elevated levels of ALT and AST activities, lipid peroxidation, total bilirubin and increased total thiol and catalase contents. Notably, it significantly reduced the expression of tumor necrosis factor-alpha (TNF-α), Caspase-3 and endoplasmic reticulum (ER) inositol-requiring enzyme 1(IRE1) mRNAs, which is an ER trans membrane sensor that activates the unfolded protein response (UPR) to maintain the ER and cellular function.
  
  
  CONCLUSIONS
  Pretreatment with Tempol has potential hepatoprotective effects against acute liver injury, induced by CCl4, through antioxidant and anti-inflammatory activities.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Kafer Alsheikh University, Egypt. Electronic address: nabilmohie@yahoo.com.
authors.forename: N M
authors.initials: NM
authors.lastname: Abdel-Hamid
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Minia University, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Wahid
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Minia University, Egypt.
authors.forename: E M
authors.initials: EM
authors.lastname: Mohamed
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Egypt.
authors.forename: M A
authors.initials: MA
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Egypt.
authors.forename: O M
authors.initials: OM
authors.lastname: Mohafez
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Assiut University, Egypt.
authors.forename: Sally
authors.initials: S
authors.lastname: Bakar
mesh_terms: D000208:Acute Disease; D000818:Animals; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D003497:Cyclic N-Oxides; D008565:Membrane Proteins; D010880:Piperidines; D020011:Protective Agents; D012333:RNA, Messenger; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride; D002374:Catalase; C486556:Ern2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3; D005978:Glutathione; C024330:lastar A; C001803:tempol
keywords: Carbon tetrachloride; Caspase-3; IRE-1; Liver injury; TNF-α; Tempol