Quercetin decreases liver damage in mice with non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a frequent condition in obese patients that may progress to end-stage liver disease. This study was designed to evaluate the modulation of this condition by use of quercetin (Q), a flavonoid largely found in vegetable foods, with known anti-inflammatory and antioxidant properties, in the experimental model of non-alcoholic steatohepatitis (NASH) using a diet deficient in methionine and choline (MCD). Male C57BL6 mice were divided into four groups (n = 16): (i) Control plus vehicle (control ration plus carboxymethylcellulose 1% used as vehicle, CO + V); (ii) Control ration plus Q 50 mg/kg (CO + Q); (iii) MCD diet plus vehicle (NASH + V); and (iv) MCD diet plus Q (NASH + Q). Diets were administered for 4 weeks. At the end of the experimental period, liver alterations, bioindicators of oxidative stress and DNA damage were assessed. NASH was diagnosed in 100% of the mice that were fed the MCD diet. In addition, a significant increase in DNA damage in liver tissue from NASH + V group was observed in comparison with CO + V. The group NASH + Q showed a significant decrease in hepatic damage enzymes, lipoperoxidation, DNA damage and a lower degree of macrovesicular steatosis, ballooning and inflammatory process. These findings suggest that Q may have protective effects by improving liver integrity in NASH.

Quercetin treatment ameliorates inflammation and fibrosis in mice with nonalcoholic steatohepatitis.

We investigated whether quercetin protects from steatosis and limits the expression of proinflammatory and fibrogenic genes in C57BL/6J mice with nonalcoholic steatohepatitis (NASH) induced by feeding a methionine-choline-deficient (MCD) diet. Quercetin (50 mg/kg) was given by oral route daily. Mice were randomly divided into 4 groups that received for 2 or 4 wk: the control diet plus vehicle, control diet plus quercetin, MCD diet plus vehicle, and MCD diet plus quercetin. At both 2 and 4 wk, feeding the MCD diet resulted in liver steatosis, inflammatory cell accumulation, oxidative stress evaluated by the concentration of TBARS, and fibrosis evidenced by the staining of α-smooth muscle actin-positive cells in the liver. At both 2 and 4 wk, the MCD diet induced an increase in the mRNA levels of Il6, Tnf, Ptgs2, and Hmgb1 and increased the protein concentrations of Toll-like receptor-4, c-Jun terminal kinase, and p65 NFκB subunit compared with control rats. Feeding the mice the MCD diet also triggered an increase of Col1a1, Col3a1, Plod3, Tgfb1, Smad3, Smad7, Pdgfb, Ctgf, Areg, Mmp9, and Timp1 mRNA levels. These effects were totally or partially prevented by treatment with quercetin. The data obtained suggest that attenuation of multiple profibrotic and proinflammatory gene pathways contributes to the beneficial effects of quercetin in mice with MCD diet-induced steatohepatitis.

Effect of Boswellia serrata on antioxidant status in an experimental model of colitis rats induced by acetic acid.

AIM OF THE STUDY: To evaluate the antioxidant effect of an extract of the plant Boswellia serrata in an experimental model of acute ulcerative colitis induced by administration of acetic acid (AA) in rats. MATERIALS AND METHODS: The extract of B. serrata (34.2 mg/kg/day) was administered orally by gavage for 2 days before and after induction of colitis with AA diluted to 4 % and in a volume of 4 ml. RESULTS: The anal sphincter pressure in the groups treated with B. serrata showed a significant increase compared to the colitis group (P < 0.001). Histological analysis of treated animals showed less edema with preservation of mucosal crypts. Lipid peroxidation showed a significant decrease in the treated groups compared to the colitis group (P < 0.001). The superoxide dismutase (SOD) enzyme activity showed a significant reduction in the treated groups compared to the colitis group (P < 0.001), the glutathione peroxidase (GPx) significantly increased in the treated groups compared to colitis group (P < 0.05), and the same was the result for enzyme activity glutathione (GSH; P < 0.05). CONCLUSIONS: The extract of B. serrata has active antioxidant substances that exert protective effects in acute experimental colitis.

Quercetin treatment ameliorates systemic oxidative stress in cirrhotic rats.

Our aim was to investigate whether the antioxidant quercetin protects against liver injury and ameliorates the systemic oxidative stress in rats with common bile duct ligation. Secondary biliary cirrhosis was induced through 28 days of bile duct obstruction. Animals received quercetin (Q) after 14 days of obstruction. Groups of control (CO) and cirrhotic (CBDL) animals received a daily 50 mg/kg body weight i.p. injection of quercetin (CO + Q; CBDL + Q) or vehicle (CO; CBDL). Quercetin corrected the reduction in superoxide dismutase (SOD), catalase CAT, and glutathione peroxidase GPx activities and prevented the increase of thiobarbituric acid reactive substances (TBARS), aminotransferases, and alkaline phosphatase in cirrhotic animals. Quercetin administration also corrected the reduced total nitrate concentration in the liver and prevented liver fibrosis and necrosis. These effects suggest that quercetin might be a useful agent to preserve liver function and prevent systemic oxidative stress.

Suppression of amphiregulin/epidermal growth factor receptor signals contributes to the protective effects of quercetin in cirrhotic rats.

The hepatic wound-healing response to chronic noxious stimuli may lead to liver fibrosis, a key feature of the preneoplastic cirrhotic liver. Fibrogenic cells activate in response to a variety of cytokines, growth factors, and inflammatory mediators. The involvement of members of the epidermal growth factor family in this process has been suggested. Amphiregulin is an epidermal growth factor receptor (EGFR) ligand specifically induced upon liver injury. We investigated the effects of quercetin on the amphiregulin/EGFR signal and on the activation of downstream pathways leading to cell growth. Rats were divided into 4 groups (8 rats/group): rats subjected to common bile duct ligation (CBDL), Sham (rats subjected to simulated CBDL), quercetin-treated sham, and quercetin-treated CBDL (CBDL-Q). Quercetin (50 mg/kg i.p. injection) was administered daily for 2 wk starting on d 14 after surgery. Overexpression of amphiregulin, EGFR, TNFα, IL-6, TGFß, platelet-derived growth factor (PDGF), extracellular regulated kinase, protein kinase B (Akt), cycloxygenase (COX)-2, and glioma-associated oncogenes (GLI)-1 and-2 were observed in liver of CBDL rats after 4 wk of bile duct ligation. CBDL-Q rats had a significantly diminished expression of amphiregulin and EGFR compared with untreated CBDL rats. Furthermore, mRNA levels of TNFα, IL-6, TGFß, and PDGF and the protein content of COX-2, GLI-1, and GLI-2 were significantly lower in CBDL-Q rats than in untreated CBDL rats. The findings indicate that quercetin ameliorated activation of survival pathways and downregulated the expression of genes related to inflammation and precancerous conditions. Suppression of amphiregulin/EGFR signals may contribute to this effect.

Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis.

CONTEXT: Non-alcoholic steatohepatitis is a disease with a high incidence, difficult diagnosis, and as yet no effective treatment. So, the use of experimental models for non-alcoholic steatohepatitis induction and the study of its routes of development have been studied. OBJECTIVES: This study was designed to develop an experimental model of non-alcoholic steatohepatitis based on a methionine- and choline-deficient diet that is manufactured in Brazil so as to evaluate the liver alterations resulting from the disorder. METHODS: Thirty male C57BL6 mice divided in two groups (n = 15) were used: the experimental group fed a methionine- and choline-deficient diet manufactured by Brazilian company PragSoluções®, and the control group fed a normal diet, for a period of 2 weeks. The animals were then killed by exsanguination to sample blood for systemic biochemical analyses, and subsequently submitted to laparotomy with total hepatectomy and preparation of the material for histological analysis. The statistical analysis was done using the Student's t-test for independent samples, with significance level of 5%. RESULTS: The mice that received the methionine- and choline-deficient diet showed weight loss and significant increase in hepatic damage enzymes, as well as decreased systemic levels of glycemia, triglycerides, total cholesterol, HDL and VLDL. The diagnosis of non-alcoholic steatohepatitis was performed in 100% of the mice that were fed the methionine- and choline-deficient diet. All non-alcoholic steatohepatitis animals showed some degree of macrovesicular steatosis, ballooning, and inflammatory process. None of the animals which were fed the control diet presented histological alterations. All non-alcoholic steatohepatitis animals showed significantly increased lipoperoxidation and antioxidant enzyme GSH activity. CONCLUSION: The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in inducing steatosis and steatohepatitis in animal model, alterations that are similar to those observed in human livers.

Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis / Dieta deficiente em metionina e colina induz mudanças hepáticas características de esteatohepatite não-alcoólica

CONTEXT: Non-alcoholic steatohepatitis is a disease with a high incidence, difficult diagnosis, and as yet no effective treatment. So, the use of experimental models for non-alcoholic steatohepatitis induction and the study of its routes of development have been studied. OBJECTIVES: This study was designed to develop an experimental model of non-alcoholic steatohepatitis based on a methionine- and choline-deficient diet that is manufactured in Brazil so as to evaluate the liver alterations resulting from the disorder. METHODS: Thirty male C57BL6 mice divided in two groups (n = 15) were used: the experimental group fed a methionine- and choline-deficient diet manufactured by Brazilian company PragSoluções®, and the control group fed a normal diet, for a period of 2 weeks. The animals were then killed by exsanguination to sample blood for systemic biochemical analyses, and subsequently submitted to laparotomy with total hepatectomy and preparation of the material for histological analysis. The statistical analysis was done using the Student's t-test for independent samples, with significance level of 5 percent. RESULTS: The mice that received the methionine- and choline-deficient diet showed weight loss and significant increase in hepatic damage enzymes, as well as decreased systemic levels of glycemia, triglycerides, total cholesterol, HDL and VLDL. The diagnosis of non-alcoholic steatohepatitis was performed in 100 percent of the mice that were fed the methionine- and choline-deficient diet. All non-alcoholic steatohepatitis animals showed some degree of macrovesicular steatosis, ballooning, and inflammatory process. None of the animals which were fed the control diet presented histological alterations. All non-alcoholic steatohepatitis animals showed significantly increased lipoperoxidation and antioxidant enzyme GSH activity. CONCLUSION: The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in inducing steatosis and steatohepatitis in animal model, alterations that are similar to those observed in human livers.

CONTEXTO: A esteatohepatite não-alcoólica é uma doença com alta incidência, difícil diagnóstico e tratamentos ainda não efetivos. Com isso, o uso de modelos experimentais para indução da esteatohepatite não-alcoólica e o estudo das rotas de desenvolvimento desta doença vem sendo empregado. OBJETIVO: Desenvolver um modelo experimental de esteatohepatite não-alcoólica a partir do uso de uma dieta deficiente de metionina e colina fabricada no Brasil e avaliar as alterações hepáticas decorrentes da doença. MÉTODO: Foram utilizados 30 camundongos machos da linhagem C57BL6, onde a metade foi alimentada com dieta deficiente em metionina e colina desenvolvida no Brasil e o restante com dieta controle no período de duas semanas. Após, os animais foram mortos por exaguinação e foi realizada laparotomia com hepatectomia total e preparo do material para análise histológica, coleta de sangue para análises bioquímicas sistêmicas. O nível de significância foi 5 por cento. RESULTADOS: Os ratos que receberam a dieta deficiente em metionina e colina apresentaram perda de peso e aumento significativo das enzimas de integridade hepática e diminuição dos níveis bioquímicos sistêmicos de glicemia, triglicerídeos, colesterol total, HDL e VLDL. Todos os animais com esteatohepatite não-alcoólica mostraram, pelo menos, algum grau de esteatose macrovesicular. O diagnóstico de esteatohepatite não-alcoólica foi realizado em 100 por cento dos camundongos que receberam a dieta deficiente em metionina e colina e nenhum dos animais que recebeu dieta controle apresentou alterações histológicas. Os animais com esteatohepatite não-alcoólica apresentaram aumento de lipoperoxidação e da enzima antioxidante GSH. CONCLUSÃO:A dieta deficiente de metionina e colina desenvolvida neste estudo apresenta índices elevados de indução de esteatose e esteatohepatite em modelo animal, apresentando comportamento patológico semelhante ao humano, com custo adequado e facilidade na sua aquisição.

Lung alterations in a rat model of diabetes mellitus: effects of antioxidant therapy.

OBJECTIVE: To evaluate structural alterations of the lung in rats with diabetes mellitus (DM), by quantifying oxidative stress and DNA damage, as well as to determine the effects that exogenous superoxide dismutase (SOD) has on such alterations. METHODS: A controlled experimental study involving 40 male Wistar rats, divided into four groups (10 animals each): control; SOD-only (without DM but treated with SOD); IDM-only (with streptozotocininduced DM but untreated); and IDM+SOD (with streptozotocin-induced DM, treated with SOD). The animals were evaluated over a 60-day period, day 0 being defined as the day on which the streptozotocin-injected animals presented glycemia > 250 mg/dL. The SOD was administered for the last 7 days of that period. At the end of the study period, samples of lung tissue were collected for histopathological analysis, evaluation of tissue oxidative stress, and assessment of DNA damage. RESULTS: There were no significant differences among the groups regarding DNA damage. In the IDM-only group, there was a significant increase in the extracellular matrix and significantly greater hyperplasia of the capillary endothelium than in the SOD-only and control groups. In addition, there were significant changes in type II pneumocytes and macrophages, suggesting an inflammatory process, in the IDM-only group. However, in the IDM+SOD group, there was a reduction in the extracellular matrix, as well as normalization of the capillary endothelium and of the type II pneumocytes. CONCLUSIONS: Exogenous SOD can reverse changes in the lungs of animals with induced DM.

Alterações pulmonares em um modelo de diabetes mellitus em ratos: o efeito da terapia antioxidante / Lung alterations in a rat model of diabetes mellitus: effects of antioxidant therapy

OBJETIVO: Avaliar as alterações estruturais no pulmão de ratos com diabetes mellitus (DM) através da quantificação do estresse oxidativo e do dano ao DNA, assim como determinar os efeitos de superóxido dismutase (SOD) exógena nessas alterações. MÉTODOS: Estudo experimental controlado com 40 ratos Wistar, divididos em quatro grupos (10 animais cada): grupo controle, grupo SOD (sem DM e tratados com SOD), grupo DM (com DM induzido por estreptozotocina), e grupo DM+SOD (com DM induzido por estreptozotocina e tratados com SOD). Os animais foram avaliados por um período de 60 dias, iniciado a partir do dia em que os animais com diabetes induzido por estreptozotocina apresentaram glicemia > 250 mg/dL. Nos últimos 7 dias do período, os animais nos grupos tratados receberam SOD. Ao final do tempo de estudo, amostras de tecido pulmonar foram coletadas para análise histopatológica e avaliação do estresse oxidativo e do dano ao DNA. RESULTADOS: Não houve diferenças significativas entre os grupos em relação ao dano ao DNA. Houve um aumento significativo na matriz extracelular e hiperplasia do endotélio capilar no grupo DM quando comparado com os grupos controle e SOD. Também houve mudanças significativas em pneumócitos tipo II e macrófagos intravasculares, sugerindo um processo inflamatório no grupo DM. Entretanto, uma redução na matriz extracelular, endotélio capilar normal e pneumócitos tipo II normais foram encontrados no grupo com DM+SOD. CONCLUSÕES: A administração exógena de SOD pode reverter alterações nos pulmões de animais com DM induzido.

OBJECTIVE: To evaluate structural alterations of the lung in rats with diabetes mellitus (DM), by quantifying oxidative stress and DNA damage, as well as to determine the effects that exogenous superoxide dismutase (SOD) has on such alterations. METHODS: A controlled experimental study involving 40 male Wistar rats, divided into four groups (10 animals each): control; SOD-only (without DM but treated with SOD); IDM-only (with streptozotocininduced DM but untreated); and IDM+SOD (with streptozotocin-induced DM, treated with SOD). The animals were evaluated over a 60-day period, day 0 being defined as the day on which the streptozotocin-injected animals presented glycemia > 250 mg/dL. The SOD was administered for the last 7 days of that period. At the end of the study period, samples of lung tissue were collected for histopathological analysis, evaluation of tissue oxidative stress, and assessment of DNA damage. RESULTS: There were no significant differences among the groups regarding DNA damage. In the IDM-only group, there was a significant increase in the extracellular matrix and significantly greater hyperplasia of the capillary endothelium than in the SOD-only and control groups. In addition, there were significant changes in type II pneumocytes and macrophages, suggesting an inflammatory process, in the IDM-only group. However, in the IDM+SOD group, there was a reduction in the extracellular matrix, as well as normalization of the capillary endothelium and of the type II pneumocytes. CONCLUSIONS: Exogenous SOD can reverse changes in the lungs of animals with induced DM.

Quercetin administration ameliorates pulmonary complications of cirrhosis in rats.

In the hepatopulmonary syndrome (HPS), a common complication of liver cirrhosis, pulmonary endothelial endothelin B (ETB) receptor overexpression, enhanced endothelial nitric oxide (NO) synthase (eNOS)-derived NO production, and increases in pulmonary inducible NO synthase (iNOS) and heme oxygenase (HO-1) are important factors in the development of vasodilatation. These changes may be influenced by redox-sensitive signaling pathways, including nuclear factor-kappaB (NF-kappaB). In this study, our aim was to evaluate the effects of the flavonoid antioxidant quercetin on the development of HPS in rats with common bile duct ligation (CBDL). Rats were divided into the following 4 groups: rats subjected to CBDL, Sham (rats subjected to simulated CBDL), quercetin-treated sham, and quercetin-treated CBDL. Quercetin (50 mg/kg) was administered for 2 wk starting on d 14 after surgery. Increased NO production, overexpression of iNOS, eNOS, HO-1, and ETB-receptor and activation of NF-kappaB were observed in lung of CBDL rats. Quercetin inhibited oxidative stress, NF-kappaB activation, and the expression of different pulmonary mediators involved in HPS. Quercetin also ameliorated liver injury and reduced the expression of hepatic endothelin-1 and HO-1 in untreated cirrhotic rats. Our findings suggest that quercetin administered after the onset of hepatic injury significantly ameliorates pulmonary complications in CBDL rats and that limitation of cirrhotic evolution contributes to this effect.

Anal pressure in experimental diabetes.

PURPOSE: Diabetes mellitus is a metabolic endocrine disorder that affects many systems, the gastrointestinal system often being among the affected systems. This experimental study work was designed to demonstrate altered anal sphincter pressures in an experimental model of diabetes mellitus (DM). MATERIALS AND METHODS: Male Wistar rats (mean weight = 250 g) were used and randomized in two groups (n = 10): CO = control and DM. DM was induced by administering a single dose of streptozotocin. Glycemic levels were measured at the start (time = 0) and end (time = 60) of the experiment and anorectal manometry at the end. RESULTS: DM rats presented a significant increase in glycemia at day 60 (DM = 407.14 +/- 73.76) as compared to the control group (time 0 = 175.7 +/- 18.62 and time 60 = 198.04 +/- 28.66). Anorectal manometry showed a significant decrease in anal pressure in the DM group at day 60 (DM = 34.2 +/- 4.97) as compared to the CO group at the same time (CO = 67.4 +/- 2.06), with P < 0.01 and P < 0.001 (Student's t test). CONCLUSIONS: The results suggest that DM, due to the high glycemic levels, lead to alterations such as anal sphincter hypotony, which may cause complications such as fecal incontinence.

[Experimental models for assessment of pulmonary alterations in hepatopulmonary syndrome]. / Modelos experimentais para avaliação das alterações pulmonares na síndrome hepatopulmonar.

OBJECTIVE: The aim of this study was to identify the best experimental model in which to observe the pulmonary alterations characterizing hepatopulmonary syndrome (HPS). METHODS: Male Wistar rats, with mean weight of 250 g, were used in four experimental models: inhaled carbon tetrachloride; intraperitoneal carbon tetrachloride; partial portal vein ligation; and bile duct ligation (BDL). The animals in all groups were divided into control and experimental subgroups. The following variables were measured: transaminase levels; blood gases; lipoperoxidation, using thiobarbituric acid reactive substances (TBARS) and chemiluminescence; and levels of superoxide dismutase (SOD) anti-oxidant activity. Anatomopathological examination of the lung was also performed. RESULTS: There were statistically significant differences between the BDL control and BDL experimental groups: aspartate aminotransferase (105.3 +/- 43 vs. 500.5 +/- 90.3 IU/L); alanine aminotransferase (78.75 +/- 37.7 vs. 162.75 +/- 35.4 IU/L); alkaline phosphatase (160 +/- 20.45 vs. 373.25 +/- 45.44 IU/L); arterial oxygen tension (85.25 +/- 8.1 vs. 49.9 +/- 22.5 mmHg); and oxygen saturation (95 +/- 0.7 vs. 73.3 +/- 12.07%). Lipoperoxidation and antioxidant activity also differed significantly between the two BDL groups (control vs. experimental): TBARS (0.87 +/- 0.3 vs. 2.01 +/- 0.9 nmol/mg protein); chemiluminescence (16008.41 +/- 1171.45 vs. 20250.36 +/- 827.82 cps/mg protein); and SOD (6.66 +/- 1.34 vs. 16.06 +/- 2.67 IU/mg protein). The anatomopathological examination confirmed pulmonary vasodilatation in the BDL model. In the other models, there were no alterations that were characteristic of HPS. CONCLUSIONS: The data obtained suggest that the BDL model can be used in future studies involving hepatic alterations related to oxidative stress and HPS.

Modelos experimentais para avaliação das alterações pulmonares na síndrome hepatopulmonar / Experimental models for assessment of pulmonary alterations in hepatopulmonary syndrome

OBJETIVO: O objetivo deste trabalho foi avaliar o melhor modelo experimental para observar alterações pulmonares que caracterizam a síndrome hepatopulmonar (SHP). MÉTODOS: Ratos machos Wistar, com peso médio de 250 g foram usados em quatro modelos experimentais: tetracloreto de carbono inalatório; tetracloreto de carbono intraperitoneal; ligadura parcial de veia porta; e ligadura de ducto biliar (LDB). Em todos os grupos os animais foram divididos em controle e experimental. Foram avaliadas as seguintes variáveis: transaminases; gasometria; lipoperoxidação por substâncias que reagem ao ácido tiobarbitúrico (TBARS) e por quimiluminescência; e atividade antioxidante da enzima superóxido dismutase (SOD). Foi feito também o exame anatomopatológico do pulmão. RESULTADOS: Observou-se diferenças significativas entre os grupos LDB controle e experimental: aspartato amino transferase (105,3 ± 43 vs. 500,5 ± 90,3 UI/L); alanino aminotransferase (78,75 ± 37,7 vs. 162,75 ± 35,4 UI/L); fosfatase alcalina (160 ± 20,45 vs. 373,25 ± 45,44 UI/L); pressão parcial de oxigênio (85,25 ± 8,1 vs. 49,9 ± 22,5 mmHg); e saturação de hemoglobina (95 ± 0,7 vs. 73,3 ± 12,07 por cento). A lipoperoxidação e a atividade antioxidante também demonstrou diferenças entre os dois grupos LDB (controle vs. experimental): TBARS (0,87 ± 0,3 vs. 2,01 ± 0,9 nmol/mg proteína); quimiluminescência (16008,41 ± 1171,45 vs. 20250,36 ± 827,82 cps/mg proteína); e SOD (6,66 ± 1,34 vs. 16,06 ± 2,67 UI/mg proteína). No exame anatomopatológico observou-se vasodilatação pulmonar no modelo de LDB. CONCLUSÕES: Os dados sugerem que o modelo de LDB pode ser usado para outros estudos envolvendo alterações hepáticas e suas relações com o estresse oxidativo e a SHP.

OBJECTIVE: The aim of this study was to identify the best experimental model in which to observe the pulmonary alterations characterizing hepatopulmonary syndrome (HPS). METHODS: Male Wistar rats, with mean weight of 250 g, were used in four experimental models: inhaled carbon tetrachloride; intraperitoneal carbon tetrachloride; partial portal vein ligation; and bile duct ligation (BDL). The animals in all groups were divided into control and experimental subgroups. The following variables were measured: transaminase levels; blood gases; lipoperoxidation, using thiobarbituric acid reactive substances (TBARS) and chemiluminescence; and levels of superoxide dismutase (SOD) anti-oxidant activity. Anatomopathological examination of the lung was also performed. RESULTS: There were statistically significant differences between the BDL control and BDL experimental groups: aspartate aminotransferase (105.3 ± 43 vs. 500.5 ± 90.3 IU/L); alanine aminotransferase (78.75 ± 37.7 vs. 162.75 ± 35.4 IU/L); alkaline phosphatase (160 ± 20.45 vs. 373.25 ± 45.44 IU/L); arterial oxygen tension (85.25 ± 8.1 vs. 49.9 ± 22.5 mmHg); and oxygen saturation (95 ± 0.7 vs. 73.3 ± 12.07 percent). Lipoperoxidation and antioxidant activity also differed significantly between the two BDL groups (control vs. experimental): TBARS (0.87 ± 0.3 vs. 2.01 ± 0.9 nmol/mg protein); chemiluminescence (16008.41 ± 1171.45 vs. 20250.36 ± 827.82 cps/mg protein); and SOD (6.66 ± 1.34 vs. 16.06 ± 2.67 IU/mg protein). The anatomopathological examination confirmed pulmonary vasodilatation in the BDL model. In the other models, there were no alterations that were characteristic of HPS. CONCLUSIONS: The data obtained suggest that the BDL model can be used in future studies involving hepatic alterations related to oxidative stress and HPS.

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.

Evaluation of respiratory muscle strength and pulmonary function in heart failure patients.

BACKGROUND: Heart failure (HF) is the inability of the heart to pump enough blood to supply the necessities of the body. Pulmonary function and respiratory muscles can be affected and typical symptoms presented by the patients include discomfort at a minimal exertion. OBJECTIVE: To verify pulmonary function and respiratory muscle strength in patients with class II and III HF as defined by the New York Heart Association (NYHA). METHODS: The study was descriptive and observational, and comprised 12 class II and III HF patients in follow-up at the out-patient. Pulmonary function assessments [Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC)] were performed using microspirometry and respiratory muscle strength [Maximal Expiratory Pressure (MEPmax) and Maximal Inspiratory Pressure (MIPmax)] were evaluated using a pressure transducer (Globalmed). RESULTS: Differences were found between the functional classes II and III in relation to pulmonary function: FEV1 (II: 91.17 +/- 19.87; III: 68.17 +/- 21.78); FVC (II: 68.17 +/- 21.78; III: 73.67 +/- 22.94); and respiratory muscle strength: MIPmax (II: 71.67 +/- 40.70; III: 53.33 +/- 29.27) and MEPmax (II: 98.83 +/- 34.56; III: 58.33 +/- 15.06). The class II were higher for all study parameters, only MEPmax revealed a statistically significant difference. CONCLUSION: The pulmonary function and respiratory muscle strength are impaired in heart failure patients class III patients, particularly in relation to MEPmax.

Avaliação da força muscular respiratória e da função pulmonar em pacientes com insuficiência cardíaca / Evaluation of respiratory muscle strength and pulmonary function in heart failure patients

FUNDAMENTO: O termo insuficiência cardíaca (IC) refere-se à falha do coração em bombear sangue para suprir as necessidades do organismo. A função pulmonar e os músculos respiratórios podem estar afetados e os sintomas típicos apresentados pelos pacientes são desconforto aos mínimos esforços. OBJETIVO: Verificar a função pulmonar e a força dos músculos respiratórios em pacientes com IC em classes funcionais II e III, segundo a New York Heart Association (NYHA). MÉTODOS: O estudo foi descritivo e observacional, sendo incluídos 12 indivíduos com IC em classes II e III que estavam em acompanhamento ambulatorial. A função pulmonar (volume expiratório forçado no primeiro segundo - VEF1 - e capacidade vital forçada - CVF) foi avaliada por meio da microespirometria e a força muscular respiratória (pressão expiratória máxima - PEmáx - e pressão inspiratória máxima - PImáx), por meio de manovacuometria (marca Globalmed®). RESULTADOS: Houve diferença entre as classes II e III em relação à função pulmonar (VEF1: II = 91,17 ± 19,87 e III = 68,17 ± 21,78; CVF: II = 68,17 ± 21,78 e III = 73,67 ± 22,94) e à força muscular respiratória (PImáx: II = 71,67 ± 40,70 e III = 53,33 ± 29,27; PEmáx: II = 98,83 ± 34,56 e III = 58,33 ± 15,06). A classe II apresentou valores maiores que a III, em todos os parâmetros avaliados, com diferença estatisticamente significativa na PEmáx. CONCLUSÃO: A função pulmonar e a força muscular respiratória estão prejudicadas na IC, onde os indivíduos da classe III apresentam valores menores que a II, principalmente na PEmáx.

BACKGROUND: Heart failure (HF) is the inability of the heart to pump enough blood to supply the necessities of the body. Pulmonary function and respiratory muscles can be affected and typical symptoms presented by the patients include discomfort at a minimal exertion. OBJECTIVE: To verify pulmonary function and respiratory muscle strength in patients with class II and III HF as defined by the New York Heart Association (NYHA). METHODS: The study was descriptive and observational, and comprised 12 class II and III HF patients in follow-up at the out-patient. Pulmonary function assessments [Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC)] were performed using microspirometry and respiratory muscle strength [Maximal Expiratory Pressure (MEPmax) and Maximal Inspiratory Pressure (MIPmax)] were evaluated using a pressure transducer (Globalmed™). RESULTS: Differences were found between the functional classes II and III in relation to pulmonary function: FEV1 (II: 91.17±19.87; III: 68.17±21.78); FVC (II: 68.17±21.78; III: 73.67±22.94); and respiratory muscle strength: MIPmax (II: 71.67±40.70; III: 53.33±29.27) and MEPmax (II: 98.83±34.56; III: 58.33±15.06). The class II were higher for all study parameters, only MEPmax revealed a statistically significant difference. CONCLUSION: The pulmonary function and respiratory muscle strength are impaired in heart failure patients class III patients, particularly in relation to MEPmax.

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 ± 43/Ci = 500,5 ± 90,3 alanina aminotransferase, Co = 78,75 ± 37,7/Ci = 162,75 ± 35,4 e fosfatase alcalina, Co = 160 ± 20,45/Ci = 373,25 ± 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 ± 0,3/Ci = 2,01 ± 0,9; quimiluminescência Co = 16008,41 ± 1171,45/Ci = 20250,36 ± 827,82; superóxido dismutase Co = 6,66 ± 1,34/Ci = 16,06 ± 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.

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

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 +/- 43/Ci = 500.5 +/- 90.3, alanine aminotransferase, Co = 78.75 +/- 37.7/Ci = 162.75 +/- 35.4, and alkaline phosphatase, Co = 160 +/- 20.45/Ci = 373 +/- 45.44. The lipoperoxidation and the antioxidant response had significant differences between the groups when evaluated in lung (lipoperoxidation) Co = 0.87 +/- 0.3/Ci = 2.01 +/- 0.9, chemoluminescence Co = 16008.41 +/- 1171.45/Ci = 20250.36 +/- 827.82 superoxide dismutase Co = 6.66 +/- 1.34/Ci = 16.06 +/- 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.