title: Effects of sulfasalazine on lipid peroxidation and histologic liver damage in a rat model of obstructive jaundice and obstructive jaundice with lipopolysaccharide-induced sepsis.
abstract: BACKGROUND
  Sulfasalazine, an inhibitor of cyclooxygenase, 5-lipoxygenase, and nuclear factor κB (NF-κB), has been found to alleviate oxidative damage, proinflammatory cytokine production, bile-duct proliferation, neutrophil infiltration, and fibrosis. Therefore, it may have a potential effect in attenuating lipid peroxidation and histologic liver damage in patients with biliary obstruction and biliary obstruction with sepsis.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect of sulfasalazine on lipid peroxidation and histologic liver damage due to obstructive jaundice (OJ) and to OJ with lipopolysaccharide (LPS)-induced sepsis in an experimental model.
  
  
  METHODS
  Male Wistar rats, weighing 150 to 220 g, were randomized into 6 groups: OJ; OJ + LPS; OJ + sulfasalazine; OJ + sulfasalazine + LPS (sulfasalazine administered before sepsis); OJ + LPS + sulfasalazine (sulfasalazine administered after sepsis); and sham. Liver malondialdehyde (MDA) and myeloperoxidase (MPO) activities were assessed to monitor lipid peroxidation and neutrophil infiltration in liver tissue. Histologic liver damage was evaluated with hematoxylin-eosin stained slides. Liver tissue NF-κB and caspase-3 expression were studied immunohistopathologically to evaluate lipid peroxidation, liver damage, and hepatocyte apoptosis.
  
  
  RESULTS
  Forty-eight rats were evenly randomized into 6 groups of 8. MDA (P = 0.001), MPO (P = 0.001), NF-κB (P = 0.003), caspase-3 expression (P = 0.002), and liver injury scores (P = 0.002) increased significantly in the OJ group compared with the sham group. Compared with the OJ group, MDA (P = 0.030) and MPO levels (P = 0.001), and liver injury scores (P = 0.033) were decreased significantly in the OJ + sulfasalazine group. In the OJ + sulfasalazine + LPS and OJ + LPS + sulfasalazine groups, MDA (P = 0.008 and P = 0.023, respectively) and MPO (both, P = 0.001) were significantly decreased; however, liver NF-κB, caspase-3 expression, and liver injury scores were not significantly different compared with the OJ + LPS group. There was no significant difference between the OJ + LPS + sulfasalazine and OJ + sulfasalazine + LPS groups in regard to all end points when comparing the effects of sulfasalazine administered before or after sepsis.
  
  
  CONCLUSIONS
  Sulfasalazine was associated with decreased neutrophil accumulation and lipid peroxidation in these rats with OJ. Administration of sulfasalazine before or after LPS-induced sepsis was associated with a reduction in lipid peroxidation and neutrophil accumulation; however, it did not attenuate histologic liver damage. There was no difference between the findings when sulfasalazine was administered before or after sepsis in OJ.
authors.affiliation: Department of General Surgery, Mersin University Medical School, Mersin, Turkey.
authors.forename: Musa
authors.initials: M
authors.lastname: Dirlik
authors.affiliation: Department of General Surgery, Mersin University Medical School, Mersin, Turkey.
authors.forename: Aydin
authors.initials: A
authors.lastname: Karahan
authors.affiliation: Department of General Surgery, Mersin University Medical School, Mersin, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Canbaz
authors.affiliation: Department of General Surgery, Mersin University Medical School, Mersin, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Caglikulekci
authors.affiliation: Department of Pathology, Mersin University Medical School, Mersin, Turkey.
authors.forename: Ayşe
authors.initials: A
authors.lastname: Polat
authors.affiliation: Department of Biochemistry, Mersin University Medical School, Mersin, Turkey.
authors.forename: Lulufer
authors.initials: L
authors.lastname: Tamer
authors.affiliation: Department of General Surgery, Mersin University Medical School, Mersin, Turkey.
authors.forename: Suha
authors.initials: S
authors.lastname: Aydin
keywords: caspase-3; lipid peroxidation; liver injury; nuclear factor κB; sulfasalazine