N-acetylcysteine effects on genotoxic and oxidative stress parameters in cirrhotic rats with hepatopulmonary syndrome.
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.
Vercelino
Rafael
R
Laboratory of Experimental Hepatology and Physiology, Porto Alegre Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Tieppo
Juliana
J
Dias
Alexandre Simões
AS
Marroni
Cláudio Augusto
CA
Garcia
Eduardo
E
Meurer
Luise
L
Picada
Jaqueline Nascimento
JN
Marroni
Norma Possa
NP
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D020552:Comet Assay; D003135:Common Bile Duct / Q000601:surgery; D004249:DNA Damage; D020065:Hepatopulmonary Syndrome / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008026:Ligation; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D009566:Nitrates; D009573:Nitrites; D013482:Superoxide Dismutase; D000111:Acetylcysteine