Erdosteine treatment attenuates oxidative stress and fibrosis in experimental biliary obstruction.
Oxidative stress, in particular lipid peroxidation, induces collagen synthesis and causes fibrosis. The aim of this study was to assess the antioxidant and antifibrotic effects of erdosteine on liver fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in Wistar albino rats by bile duct ligation (BDL). Erdosteine (10 mg/kg, orally) or saline was administered for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver functions and tissue damage, respectively. Pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6 and antioxidant capacity (AOC) were assayed in plasma samples. Liver tissues were taken for determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence assay. Serum AST, ALT, LDH, and plasma cytokines were elevated in the BDL group as compared to controls and were significantly decreased by erdosteine treatment. Hepatic GSH level and plasma AOC, depressed by BDL, were elevated back to control level with erdosteine treatment. Furthermore, hepatic luminol and lucigenin chemiluminescence (CL), MDA level, MPO activity and collagen content in BDL group increased dramatically compared to control and reduced by erdosteine treatment. Since erdosteine administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic functions, it seems likely that erdosteine with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.
Sener
Göksel
G
School of Pharmacy, Department of Pharmacology, Marmara University, Tibbiye Cad, 34668, Istanbul, Turkey. gsener@marmara.edu.tr
Sehirli
A Ozer
AO
Toklu
Hale Z
HZ
Yuksel
Meral
M
Ercan
Feriha
F
Gedik
Nursal
N
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016207:Cytokines / Q000097:blood; D005100:Expectorants / Q000627:therapeutic use*; D005978:Glutathione / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D003012:Microbial Collagenase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D013864:Thioglycolates / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*
D016207:Cytokines; D005100:Expectorants; D013864:Thioglycolates; D013876:Thiophenes; D008315:Malondialdehyde; C048498:erdosteine; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003012:Microbial Collagenase; D005978:Glutathione