Antioxidant effect of N-acetylcysteine on prehepatic portal hypertensive gastropathy in rats

Background. Portal hypertension is a clinical syndrome associated with the development of a hyperdynamic circulation and gastroesophageal varices.Aim. To evaluate the antioxidant effect of N-acetylcysteine on portal hypertensive rats.Material and methods. Portal hypertension was induced by partial portal vein ligation (PPVL). Oxidative damage in the stomach was measured by lipoperoxidation trough thiobarbituric acid reactive substances (TBARS) and antioxidant enzyme activity; we also evaluated nitrates and nitrites level and histology stained by hematoxylin-eosin. We performed evaluation of portal pressure and measurement of vessels diameter. Liver damage was evaluated by measuring hepatic enzymes. The animals were divided in four experimental groups (n = 6): Sham-operated (SO), SO + NAC, Partial portal vein ligation (PPVL) and PPVL + NAC. N-acetylcysteine (10 mg/kg ip) was administered daily for 7 days and started 8 days after surgery.Results. The portal hypertensive group showed an increase in portal pressure, vessels diameter, levels of TBARS and nitrates and nitrites when compared to SO group. These values were accompanied by a decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant enzyme activity. Histology showed dilated vessels in the gastric mucosa in the PPVL group. NAC was able to decrease portal pressure values, vessels diameter, TBARS and also nitrates and nitrites levels when compared to PPVL group. Furthermore, PPVL+NAC group presented an increase in SOD and GPx activity. N-acetylcysteine attenuated damage in gastric mucosa.Conclusion. Oxidative stress is associated with portal hypertension and that antioxidant NAC is able to minimize damages of PPVL in rats

EFEITO DA N-ACETILCISTEÍNA (NAC) SOBRE O ESTRESSE OXIDATIVO NO MODELO EXPERIMENTAL DE CIRROSE

A cirrose induzida por tetracloreto de carbono (CCl4) é um modelo experimental clássico que simula asalterações da doença em humanos. A cirrose apresenta alterações nos mecanismos antioxidantes, com umdesequilíbrio nos processos oxirredutivos. A NAC é um antioxidante sintético com diversas aplicações nosúltimos quarenta anos, como tratamento de bronquite crônica, fibrose cística, choque séptico, SARA, eintoxicações com paracetamol. O objetivo deste estudo foi avaliar a ação protetora da NAC sobre o estresseoxidativo em fígados de ratos cirróticos por inalalação de CCl4, utilizando a peroxidação lipídica, as provasde função hepática e a histologia dos fígados dos animais. Foram utilizados 41 ratos Wistar machos, compeso médio de 250g, divididos em 4 grupos: Controle (CO); Controle Tratado (CO + NAC); Cirrótico(CCl4); Cirrótico Tratado (CCl4+NAC). Os animais foram submetidos a inalações de CCl4 (2x porsemana) durante 13 semanas. Todos os grupos receberam fenobarbital na água de beber (0,3g/L), a fim deacelerar o metabolismo do CCl4. A dose de NAC foi de 10 mg/Kg/dia i.p.. A análise estatística utilizada foiANOVA e teste “t” de Student (p0,05). A determinação da lipoperoxidação foi avaliada através dequimiluminescência e TBARS, demonstrando maior dano de membranas celulares no grupo CCl4 (p0,01) e indicando dano reduzido no grupo CCl4+NAC, que obteve valores semelhantes aos do controle.provas de função hepática (AST, ALT, BT, BD, Albumina, FA) sugeriram um aumento significativolesão tecidual no grupo CCl4, quando comparado aos demais (p0,001). Na análise histológica por Picrosírius,os animais cirróticos apresentaram fibrose severa, enquanto o grupo cirrótico tratado apresentou fibrosea moderada. Os dados obtidos sugerem que a NAC oferece proteção ao fígado de ratos cirróticos

Exercise capacity of cirrhotic patients with hepatopulmonary syndrome

Introduction. Hepatopulmonary syndrome (HPS) is characterized by a clinical triad of liver disease and/or portal hypertension, intrapulmonary vascular dilatation and abnormal arterial oxygenation. These conditions can worsen muscle strength, exercise capacity and functionality in the affected population.Objective. The objective of this study was to compare exercise capacity, functional condition and respiratory muscle strength in cirrhotic patients diagnosed with HPS and cirrhotic patients without this diagnosis.Material and methods. This cross-sectional study used a convenience sample consisting of 178 patients (92 patients with HPS and 86 patients without HPS) with a diagnosis of liver cirrhosis caused by either alcohol consumption or the hepatitis C virus (HCV). Peak oxygen consumption (VO2 peak) was used to verify exercise capacity, the six-minute walk test (6MWT) was used to test functionality, and manovacuometry was used to evaluate the strength of the respiratory muscles. The Kolmogorov-Smirnov test and Student’s t-test were used for the statistical analysis. The data were analyzed using SPSS 16.00, and p < 0.05 was considered significant.Results. The group of patients with the diagnosis of HPS exhibited a lower VO2 peak (14.2 ± 2.3 vs. 17.6 ± 2.6, p < 0.001), shorter distance walked in the 6MWT (340.8 ± 50.9 vs. 416.5 ± 91.4, p < 0.001), lower maximal inspiratory pressure (-49.1 ± 9.8 vs. -74.2 ± 13.9, p = 0.001) and lower maximum expiratory pressure (60.1 ± 12.2 vs. 76.8 ± 14.7, p = 0.001).Conclusion. The group of cirrhotic patients diagnosed with HPS exhibited lower values for VO2 peak, distance walked in the 6MWT and respiratory muscle strength than the cirrhotic patients not diagnosed with HPS

Ligadura de ducto biliar como modelo de estudo da síndrome hepatopulmonar e estresse oxidativo Common bile duct ligation as a model of hepatopulmonary syndrome and oxidative stress

RACIONAL: A síndrome hepatopulmonar é caracterizada por uma disfunção hepática e pela existência de dilatações dos vasos pulmonares, levando a alterações nas trocas gasosas, tendo algumas das suas características observadas de forma experimental no modelo de ligadura de ducto biliar. OBJETIVOS: Avaliar o estresse oxidativo no tecido pulmonar de ratos cirróticos por ligadura de ducto biliar comum. MATERIAIS E MÉTODOS: Foram utilizados 12 ratos machos Wistar, pesando entre 200 e 300 g, divididos em dois grupos: controles (Co = 6) e cirróticos (Ci = 6). Foram realizadas avaliações de transaminases, gasometria arterial, avaliação da lipoperoxidação (substâncias reativas ao ácido tiobarbitúrico e quimiluminescência) e quantificação da atividade enzimática antioxidante através das concentrações da enzima superóxido dismutase. Os tecidos analisados para avaliação da síndrome hepatopulmonar foram o fígado cirrótico e o pulmão. RESULTADOS: Os animais com ligadura de ducto biliar apresentaram alteração nas transaminases: aspartato aminotransferase, Co = 105,3 &plusmn; 43/Ci = 500,5 &plusmn; 90,3 alanina aminotransferase, Co = 78,75 &plusmn; 37,7/Ci = 162,75 &plusmn; 35,4 e fosfatase alcalina, Co = 160 &plusmn; 20,45/Ci = 373,25 &plusmn; 45,44. Em relação à lipoperoxidação e à resposta antioxidante, estas também apresentaram diferenças estatisticamente significativas quando avaliadas no pulmão (substâncias reativas ao ácido tiobarbitúrico) Co = 0,87 &plusmn; 0,3/Ci = 2,01 &plusmn; 0,9; quimiluminescência Co = 16008,41 &plusmn; 1171,45/Ci = 20250,36 &plusmn; 827,82; superóxido dismutase Co = 6,66 &plusmn; 1,34/Ci = 16,06 &plusmn; 2,67. CONCLUSÕES: Os dados obtidos sugerem que no modelo experimental de cirrose por ligadura de ducto biliar há aumento significativo da lipoperoxidação no tecido pulmonar, bem como aumento na atividade da enzima antioxidante superóxido dismutase, sugerindo a presença de dano pulmonar decorrente da cirrose biliar secundária.<br>BACKGROUND: The hepatopulmonary syndrome is characterized by hepatic dysfunction and presence of dilated pulmonary vessels, with alterations in air diffusion that can be demonstrated in the experimental model of common bile duct ligation. AIM: To evaluate the oxidative stress in pulmonary tissue of cirrhotic rats with common bile duct ligation. MATERIAL/METHODS: We used 12 male Wistar rats weighing between 200-300 g divided in two groups: control (Co = 6) and cirrhotic (Ci = 6). We evaluated aminotransferases, arterial gasometry, lipoperoxidation and chemoluminescence), and antioxidant enzymatic activity with superoxide dismutase. The tissues analyzed for hepatopulmonary syndrome were cirrhotic liver and lung. RESULTS: The animals with common bile duct ligation showed alterations in the following aminotransferases: aspartate aminotransferase, Co = 105.3 &plusmn; 43/Ci = 500.5 &plusmn; 90.3, alanine aminotransferase, Co = 78.75 &plusmn; 37.7/Ci = 162.75 &plusmn; 35.4, and alkaline phosphatase, Co = 160 &plusmn; 20.45/Ci = 373 &plusmn; 45.44. The lipoperoxidation and the antioxidant response had significant differences between the groups when evaluated in lung (lipoperoxidation) Co = 0.87 &plusmn; 0.3/Ci = 2.01 &plusmn; 0.9, chemoluminescence Co = 16008.41 &plusmn; 1171.45/Ci = 20250.36 &plusmn; 827.82 superoxide dismutase Co = 6.66 &plusmn; 1.34/Ci = 16.06 &plusmn; 2.67. CONCLUSIONS: Our results suggest that in this experimental model of cirrhosis using common bile duct ligation, there is an increase in lipoperoxidation in pulmonary tissue as well as an increase in superoxide dismutase's antioxidant activity, suggesting a pulmonary injury caused by secondary biliary cirrhosis