N-Acetylcysteine Effects on Genotoxic and Oxidative Stress Parameters in Cirrhotic Rats with Hepatopulmonary Syndrome

Laboratory of Experimental Hepatology and Physiology, Porto Alegre Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Basic & Clinical Pharmacology & Toxicology (Impact Factor: 2.38). 05/2008; 102(4):370-6. DOI: 10.1111/j.1742-7843.2007.00181.x
Source: PubMed


The aim of this study was to evaluate the potential antioxidant effects of N-acetylcysteine in hepatopulmonary syndrome, a complication of cirrhosis, using an experimental model of common bile duct ligation in rats. Male Wistar rats were divided into four experimental groups: CBDL (animals submitted to common bile duct ligation); Sham (animals submitted to simulated common bile duct ligation); Sham + N-acetylcysteine, and CBDL + N-acetylcysteine. N-acetylcysteine (10 mg/kg, intraperitoneally) was administered for 2 weeks starting on day 14 after surgery. Some alterations in the liver integrity were investigated by evaluation of serum enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and arterial blood gases. Lipoperoxidation by thiobarbituric acid-reactive substances assay, superoxide dismutase activity and total nitrates was measured as parameters of oxidative stress, performed on lung homogenates. Micronucleus assay in bone marrow and comet assay in lung, liver and blood were performed to assess the genotoxic effects by oxidative stress. The results showed an improvement in the enzymatic parameters and arterial blood gases, a reduction of lipoperoxidation and in the total nitrates after treatment with N-acetylcysteine. Histological analysis showed vasodilatation in the lung, which was reversed by N-acetylcysteine. Micronuclei frequency and DNA damage in lung and liver were increased in the CBDL group. N-Acetylcysteine caused no genotoxic effect and did not influence the induction of micronucleus in bone marrow and DNA damage in lung and liver. The results suggest protective effects after treatment with N-acetylcysteine in cirrhotic rats with hepatopulmonary syndrome.

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Available from: Norma Possa Marroni, Nov 02, 2014
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    • "Mesenteric artery ROS in cirrhotic rats, especially O2.-, exhibit a significantly higher intracellular concentration 28-30. Meanwhile, superoxide dismutase (SOD) cannot penetrate the cell membrane and reduces intracellular O2.- level 18. Tempol, a superoxide dismutase mimic, can freely enter the cell, react and degrade with O2.- subsequently, thus protecting cells from oxidative damage 31. "
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    International journal of biological sciences 03/2014; 10(4):386-95. DOI:10.7150/ijbs.8081 · 4.51 Impact Factor
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    • "N-acetyl cysteine, an inhibitor of reactive oxygen species, has been shown to attenuate HPS in rat models of cirrhosis [83]. Improvement of arterial blood gases and reversal of pulmonary vasodilatation in pathology was observed in the study. "
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    ABSTRACT: Aim: Hepatopulmonary syndrome is a pulmonary dysfunction in the context of liver cirrhosis characterized by arterial deoxygenation. Affected patients have increased morbidity and mortality, and many of them expire before undergoing liver transplantation. Therefore, finding medical therapy as a bridge to transplantation or as a final treatment is necessary. In this study, we aimed to review the current literature about pharmacological options available for treatment of hepatopulmonary syndrome. Methods: A PubMED and Scopus search was conducted in January 2013 on the English literature published in any time period to find human and animal studies reporting pharmacological therapy of hepatopulmonary syndrome. Results: Out of 451 studies, 29 relevant articles were included. The number of patients, type, dose, duration, and mechanism of drugs in these studies was extracted and summarized separately. Most of pharmacologic agents act through inhibition of nitric oxide synthase and reduction in nitric oxide production, inactivation of endothelin-1, and treatment of bacterial translocation and pulmonary angiogenesis. Conclusion: Several drugs have been applied for the treatment of HPS with conflicting results. However, no large randomized trial has been conducted probably due to low number of patients. Multicentered clinical trials are necessary to investigate these drugs.
    BioMed Research International 09/2013; 2013:670139. DOI:10.1155/2013/670139 · 2.71 Impact Factor
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    • "Therefore in this study we focused on two antioxidants N-acetylcysteine (NAC) and trolox that have been found to reduce oxidative stress and inflammation. NAC is a membrane-permeable thiolic compound that contains a sulfhydryl group donor, serving as a precursor of glutathione (GSH) synthesis and inhibits the formation of reactive oxygen species (ROS) [14], [15]. NAC has been shown to exhibit protective effects against DNA oxidative damage by its antioxidant properties [16], [17]. "
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    PLoS ONE 12/2011; 6(12):e26059. DOI:10.1371/journal.pone.0026059 · 3.23 Impact Factor
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