Erdosteine treatment attenuates oxidative stress and fibrosis in experimental biliary obstruction

Abstract

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.

Pomegranate peel extract prevents liver fibrosis in biliary-obstructed rats

“…oxygen free radicals have a role in the pathogenesis of tissue injury in obstructive jaundice (Peres et al 2000;Padillo et al 2002;Sener et al 2006Sener et al , 2007. Free radical ablation for the treatment of cholestatic liver injury has been shown to have beneficial effects in the prevention of fibrosis and oxidative damage following biliary obstruction.…”

Erdosteine ameliorates the harmful effects of ischemia-reperfusion injury on the liver of rats

“…The final result is a protective effect on tissues that reduces lipid peroxidation, neutrophil infiltration and cell apoptosis mediated by noxious agents 3,28 . The hepatoprotective effect of erdosteine has also been presented in many studies [5][6][7][8][9][10][11] . Saritas et al 5 investigated the efficacy of erdosteine usage in acetaminophen-induced liver damage and compared it with N-acetyl cysteine (NAC) in the treatment and prevention of liver toxicity due to acetaminophen overdose.…”

“…Moreover, erdosteine has been shown to be effective for protecting the liver fibrosis and oxidative injury due to biliary obstruction. Sener et al 8 reported that serum AST, ALT, LDH, and plasma cytokines were elevated in the bile duct ligated (BDL) group and were significantly decreased by erdosteine treatment. It was also shown that erdosteine administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic functions, and it was suggested that these effects were associated with the antioxidant and antifibrotic properties of erdosteine.…”

“…Erdosteine also has an antiinflammatory effect which is mediated through the inhibition of LPS-induced NF-kB activation 4 . The hepatoprotective effects of erdosteine against acetaminophen-induced liver damage, cyclosporine-A-induced hepatotoxicity, experimental biliary obstruction, cisplatininduced hepatic oxidant injury, doxorubicininduced hepatotoxicity, and vancomycininduced oxidative stress in the rat liver have been shown in previous studies [5][6][7][8][9][10][11] . Erdosteine has beneficial effects on ischemia-reperfusion injury in various organs including lung, brain, kidney, intestines, ovaries, and spinal cord [12][13][14][15][16][17] .…”

The protective effect of Nigella sativa oil in the brain of the biliary obstructed rats

“…It is known that increased concentration of bile acids induce lipid peroxides, probably related to the stimulation of phagocytic activity in the polymorphonuclear leukocytes and inflammatory cells, which are present after biliary tract obstruction and enhance the tissue injury (2,3). Several clinical and experimental studies have shown that oxygen free radicals have a role in the pathogenesis of tissue injury in obstructive jaundice (4)(5)(6)(7). Thus free radical ablation for the treatment of cholestatic liver injury has been shown to have beneficial effects in the prevention of fibrosis and oxidative damage following biliary obstruction.…”