title: Investigation into the antioxidant role of arginine in the treatment and the protection for intralipid-induced non-alcoholic steatohepatitis.
abstract: BACKGROUND
  This study investigated the possible roles of arginine (Arg) in ameliorating oxidative damage of intralipid (IL)-induced steatohepatitis (NASH).
  
  
  METHODS
  NASH was induced in Sprague-Dawley rats by intravenous administration of 20 % IL for three weeks and then rats were pre- and post-treated with intraperitoneal injection of Arg for two weeks. Several biochemical parameters (blood and hepatic lipid peroxidation, glutathione, glutathione peroxidase and superoxide dismutase, hepatic cytochrome P450 2El monooxygenase (CYP2E1), nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and tumor necrosis factor-α "TNF-α") and liver histopathology were detected for rat groups.
  
  
  RESULTS
  The administration of Arg either before or after IL significantly ameliorated uncontrolled elevation of TBARS content, CYP2E1 activity (0.32 ± 0.01 or 0.3 ± 0.02 IU/mg) and TNF-α level. These effects were associated with a significant increase in the levels of glutathione, activities of antioxidant enzymes, NO level (1.649 ± 0.047 or 1.957 ± 0.073 μmol/g) and activity of hepatic eNOS (0.05 ± 0.002 or 0.056 ± 0.002 IU/mg) compared to the IL-treated rats. Moreover, the injection of Arg in NASH-induced rats showed normal hepatocytes, no steatosis and no bile duct proliferation but mild inflammation in the group which received IL after Arg.
  
  
  CONCLUSIONS
  These results proved that pre- and post-treatment with Arg blocked oxidative stress-induced NASH by inhibiting CYP2E1 activity, decreasing TNF- α level and restoration activities of eNOS and antioxidant enzymes as well as glutathione level. This antioxidant effect of Arg leads to reverse signs of liver pathology of NASH with amelioration of liver and kidney functions.
authors.affiliation: Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications (SRTA-City), New Borg El Arab, Alexandria, Egypt. marwaelhedaia@gmail.com.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Abu-Serie
authors.affiliation: Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
authors.forename: Basiouny A
authors.initials: BA
authors.lastname: El-Gamal
authors.affiliation: Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Kersh
authors.affiliation: College of Biotechnology, Misr University for Science and Technology, 6th of October City, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Saadani
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004655:Emulsions; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010743:Phospholipids; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004655:Emulsions; D010743:Phospholipids; D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; C545823:soybean oil, phospholipid emulsion; D009569:Nitric Oxide; D013024:Soybean Oil; D001120:Arginine; D005979:Glutathione Peroxidase; D019392:Cytochrome P-450 CYP2E1; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D005978:Glutathione