title: The effects of chitosan and low dose dexamethasone on extrahepatic cholestasis after bile duct ligation in Wistar rats.
abstract: Inflammation and oxidative stress are important pathways in the development of liver fibrosis following biliary obstruction.
  
  
  OBJECTIVE
  To evaluate the effects of low dose dexamethasone and chitosan, a natural compound with no side-effects, on liver damage caused by bile duct ligation in rats.
  
  
  METHODS
  Fifty female Wistar rats, randomly and equally divided in 5 groups: I (SHAM) underwent only laparotomy, II (BDL) with bile duct ligation, III (DEX) 0.125 mg/kg dexamethasone i.m. daily, IV (CS) 1 mg/kg chitosan by gavage and group V (DEX+CS), both substances. After six days, the following parameters were assessed from liver homogenates: malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), total SH groupings, nitric oxide (NO), and from plasma: MDA, γ-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB). A histopathological examination was performed using some of the elements of the Knodell Histological Activity Index.
  
  
  RESULTS
  BDL significantly increases the levels of MDA, liver enzymes, and the necro-inflammatory score compared to the sham group and it decreases the antioxidant capacity. DEX protects against lipid peroxidation and improves the antioxidant capacity, but it is not able to protect the hepatocytes. Chitosan significantly decreases (p<0.05) the levels of MDA (0.07±0.01 vs 0.10±0.01 nmoles/mg protein BDL group, p=0.027) and also ALT, TB, GGT and reduces liver necrosis and inflammation (2.75±0.95 vs 1±0, p<0.05). Both CS and DEX reduce the level of NO significantly.
  
  
  CONCLUSIONS
  BDL induces severe oxidative stress damage after six days already. Chitosan proved very efficient in protecting the hepatocytes against oxidative stress, a fact supported by the histological findings.
authors.affiliation: University of Medicine and Pharmacy Iuliu Haţieganu Department of Physiology Cluj Napoca Romania. olteanu_diana_elena@yahoo.com
authors.forename: Diana
authors.initials: D
authors.lastname: Olteanu
authors.forename: A
authors.initials: A
authors.lastname: Filip
authors.forename: A
authors.initials: A
authors.lastname: Mureşan
authors.forename: A
authors.initials: A
authors.lastname: Nagy
authors.forename: F
authors.initials: F
authors.lastname: Tabaran
authors.forename: R
authors.initials: R
authors.lastname: Moldovan
authors.forename: N
authors.initials: N
authors.lastname: Decea
authors.forename: C
authors.initials: C
authors.lastname: Catoi
authors.forename: S
authors.initials: S
authors.lastname: Clichici
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D048271:Chitosan / Q000494:pharmacology*; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008026:Ligation; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000924:Anticholesteremic Agents; D000975:Antioxidants; D005938:Glucocorticoids; D008315:Malondialdehyde; D003907:Dexamethasone; D048271:Chitosan; D005978:Glutathione