Melatonin restores zinc levels, activates the Keap1/Nrf2 pathway, and modulates endoplasmic reticular stress and HSP in rats with chronic hepatotoxicity.

BACKGROUND: Melatonin (MLT) is a potent antioxidant molecule that is shown to have a beneficial effect in various pathological situations, due to its action against free radicals. AIM: To evaluate the effect of MLT on carbon tetrachloride (CCl4) induced liver injury in rats in terms of oxidative stress, reticular stress, and cell damage. METHODS: Twenty male Wistar rats (230-250 g) were divided into four groups: Control rats, rats treated with MLT alone, rats treated with CCl4 alone, and rats treated with CCl4 plus MLT. CCl4 was administered as follows: Ten doses every 5 d, ten every 4 d, and seven every 3 d. MLT was administered intraperitoneally at a dose of 20 mg/kg from the 10th wk to the end of the experiment (16th wk). RESULTS: MLT was able to reduce the release of liver enzymes in the bloodstream and to decrease oxidative stress in CCl4 treated rats by decreasing the level of thiobarbituric acid reactive substances and increasing superoxide dismutase activity, with a lower reduction in serum zinc levels, guaranteeing a reduction in liver damage; additionally, it increased the expression of nuclear factor (erythroid-derived 2)-like 2 and decreased the expression of Kelch-like ECH-associated protein 1. MLT also decreased the expression of the proteins associated with endoplasmic reticulum stress, i.e., glucose-regulated protein 78 and activating transcription factor 6, as well as of heat shock factor 1 and heat shock protein 70. CONCLUSION: MLT has a hepatoprotective effect in an experimental model of CCl4-induced liver injury, since it reduces oxidative stress, restores zinc levels, and modulates endoplasmic reticulum stress.

Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats.

BACKGROUND: Cirrhosis is an important health problem characterized by a significant change in liver parenchyma. In animals, this can be reproduced by an experimental model of bile duct ligation (BDL). Melatonin (MLT) is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties, including its antioxidant potential. AIM: To evaluate MLT's effects on oxidative stress, the inflammatory process, and DNA damage in an experimental model of secondary biliary cirrhosis. METHODS: Male Wistar rats were divided into 4 groups: Control (CO), CO + MLT, BDL, and BDL + MLT. MLT was administered (20 mg/kg) daily beginning on day 15 after biliary obstruction. On day 29 the animals were killed. Blood samples, liver tissue, and bone marrow were collected for further analysis. RESULTS: BDL caused changes in biochemical and histological parameters and markers of inflammatory process. Thiobarbituric acid (0.46 ± 0.01) reactive substance levels, superoxide dismutase activity (2.30 ± 0.07) and nitric oxide levels (2.48 ± 0.36) were significantly lower (P < 0.001) n the groups that received MLT. DNA damage was also lower (P < 0.001) in MLT-treated groups (171.6 ± 32.9) than the BDL-only group (295.5 ± 34.8). Tissue damage and the expression of nuclear factor kappa B, interleukin-1ß, Nrf2, NQO1 and Hsp70 were significantly lower in animals treated with MLT (P < 0.001). CONCLUSION: When administered to rats with BDL-induced secondary biliary cirrhosis, MLT effectively restored the evaluated parameters.

Utility of a urine sediment score in hyperbilirubinemia/hyperbilirubinuria
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AIMS: Acute and chronic kidney dysfunction is common in patients with end-stage liver disease. Differentiation between acute kidney injury (AKI) due to hepatorenal syndrome (HRS) or acute tubular necrosis (ATN) remains difficult, however urine cast scoring systems using renal tubular epithelial cells (RTECs) and granular casts (GCs) can help to identify intrinsic kidney diseases. The objective of this study was to evaluate the urine sediment profile of patients with liver disease and hyperbilirubinemia/hyperbilirubinuria and the use of a urine sediment scoring system to identify the most common score in AKI patients and high urine bilirubin concentrations. MATERIALS AND METHODS: A retrospective study in the database of a large laboratory that assists a hospital-complex in Brazil was performed. RESULTS: Urinary casts, in particular GCs, as well as RTECs were observed more frequently in patients with hyperbilirubinemia/hyperbilirubinuria, while hyaline casts were observed in patients without hyperbilirubinemia/hyperbilirubinuria. Regardless of the AKI or non-AKI condition, the relative risk for scores 2 or 3 (sediment consistent with tubular damage, with GCs and/or RTECs in different quantities) in group 4 was 3.61 times higher compared to patients in group 1. CONCLUSION: In patients with higher urinary bilirubin levels, the urine sediment had greater numbers of GCs and RTECs and higher urine sediment scores (scores 2 or 3). The presence of a larger number of urine particles (RTECs and GCs) originating in the kidneys in the groups with higher levels of urinary bilirubin suggests an association between hyperbilirubinemia/hyperbilirubinuria and tubular injury independent of AKI or non-AKI.

Protective action of glutamine in rats with severe acute liver failure.

BACKGROUND: Severe acute liver failure (SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function. Thioacetamide (TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2 (Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative stress. AIM: To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκB-mediated inflammation in rats with TAA-induced IHAG. METHODS: Male Wistar rats (n = 28) were divided into four groups: control, control+glutamine, TAA, and TAA + glutamine. Two TAA doses (400 mg/kg) were administered intraperitoneally, 8 h apart. Glutamine (25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione (GSH), Nrf2, Kelch-like ECH-associated protein 1 (Keap1), NADPH quinone oxidoreductase1 (NQO1), superoxide dismutase (SOD)] and inflammatory process. RESULTS: TAA caused disruption of the hepatic parenchyma, with inflammatory infiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS (P < 0.001), GSH (P < 0.01), IL-1ß, IL6, and TNFα levels (P <0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP (P <0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group (P <0.01, P <0.01, and P <0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2 (P < 0.05), NQO1, and SOD (P < 0.01), as well as levels of IL-10 (P <0.001), while decreasing expression of Keap1, TLR4, NFκB (P < 0.001), COX-2 and iNOS, (P < 0.01), and reducing NO2 and NO3 levels (P < 0.05). CONCLUSION: In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway, thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation.

Antifibrogenic effect of melatonin in rats with experimental liver cirrhosis induced by carbon tetrachloride.

BACKGROUND AND AIM: Liver diseases are a major public health problem, accounting for a significant number of hospital visits and admissions and an increasing mortality rate. Melatonin (MLT) is a powerful antioxidant molecule that has been shown to be beneficial under various conditions. The objective was to evaluate the effect of MLT on experimental liver cirrhosis induced by carbon tetrachloride (CCl4) in rats. METHODS: Twenty male Wistar rats (230-250 g) were divided into four groups. I: control group (CO); II: CO + MLT; III: CCl4; and IV: CCl4 + MLT. CCl4 was administered intraperitoneally (i.p.) as follows: 10 doses every 5 days, 10 doses every 4 days, and 7 doses every 3 days. MLT was administered i.p. at a dose of 20 mg/kg from the 10th week to the end of the experiment (16th week). RESULTS: In the CCl4 + MLT group, we found that MLT caused a decrease in the level of F2-isoprostanes and NQO1 expression. We also found that MLT reduced the inflammatory process as shown by decreased expressions of NF-KB/p65 and inducible nitric oxide synthase (iNOS) and a smaller amount of inflammatory infiltrate. MLT reduced the expression of transforming growth factor beta1 (TGF-ß1), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor (VEGF). Picrosirius staining showed that MLT decreases fibrosis. CONCLUSION: MLT has a potent antifibrogenic effect, modulating the parameters of oxidative stress, angiogenesis, and inflammation.

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.

Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats.

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths throughout the world. This study was aimed to analyze oxidative stress and cell damage in a multistage model of liver carcinogenesis induced by diethylnitrosamine (DEN) in rats. Male Wistar rats weighing 145-150 g were divided into three groups: control, precancerous lesions (PL) (which received 100 mg DEN once a week every 6 weeks up to 28 weeks), and advanced HCC (50 mg DEN once/twice per week up to 19 weeks). Lipid peroxidation (TBARS), superoxide dismutase (SOD) activity, and expression of transforming growth factor-1 beta (TGF)-1ß, endothelial and inducible nitric oxide syntahese (eNOS, iNOS), NADPH quinone oxireductase (NQO)-1, nuclear factor erythroid 2-related factor (NrF)2, kelch-like ECH-associated protein (Keap)1 and heat shock protein (HSP)70 were measured. TBARS concentration was augmented in the PL and advanced HCC groups. SOD activity, TGF-1ß and Nrf2 expression were higher in animals with precancerous lesions. In advanced HCC, expression of NQO1 and iNOS increased while there was a decrease in HPS70 expression. Data obtained provide evidence for the differential activation of proteins involved in oxidative stress and cell damage during progression of carcinogenesis in an animal model of HCC.

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.

Functional status, respiratory muscle strength, and quality of life in patients with cirrhosis.

BACKGROUND: Liver diseases are responsible for metabolic disorders and loss of muscle mass and function that affect functional status and quality of life (QoL). OBJECTIVE: To compare exercise capacity, respiratory muscle strength, and QoL in liver transplant candidates with cirrhosis of the following etiologies: hepatitis C virus (HCV), hepatitis B virus (HBV), and alcoholic cirrhosis (AC). METHODS: Cross-sectional study comprising 86 patients divided into three groups: HCV (40 patients), HBV (14 patients), and AC (32 patients). Patients were evaluated using the Six-Minute Walk Test (6MWT), manometry, and the QoL questionnaire SF-36. RESULTS: The AC group showed the lowest performance in the 6MWT (meters) compared to the HBV and HCV groups (373.50 ± 50.48, 464.16 ± 32, and 475.94 ± 27.84, respectively, p=0.001). In the domains of the SF-36, the AC group had lower scores for functional capacity and physical limitations when compared to the HBV and HCV groups (p=0.001). In the comparison of respiratory muscle strength, the AC group had lower MIP (cmH2O) compared to the HBV and HCV groups (-65.54 ± 11.28, -71.61 ± 6.96, -82.44 ± 13.71, respectively, p=0.001). The MEP (cmH2O) in the AC group was also lower than in the HBV and HCV groups (65.13 ± 10.74, 82.44 ± 13.87, 83.44 ± 12.20, respectively, p=0.001). CONCLUSION: The AC group showed worse exercise capacity, respiratory muscle strength, and QoL compared to patients with HCV and HBV.

Condição funcional, força muscular respiratória e qualidade de vida em pacientes cirróticos / Functional status, respiratory muscle strength, and quality of life in patients with cirrhosis

CONTEXTUALIZAÇÃO: As doenças hepáticas são responsáveis pelas alterações metabólicas, perda da massa e função muscular que interferem na condição funcional e na qualidade de vida (QV). OBJETIVO: Comparar a capacidade ao exercício, a força muscular respiratória e a QV entre os pacientes com cirrose hepática, candidatos ao transplante de fígado, com as seguintes etiologias: hepatite vírus C (HCV), hepatite vírus B (HBV) e cirrose alcoólica (CA). MÉTODOS: Estudo transversal, composto por 86 pacientes, divididos em três grupos: HCV (40 pacientes), HBV (14 pacientes) e CA (32 pacientes). Os pacientes foram avaliados por meio do teste da caminhada de seis minutos (TC6min), manovacuometria e QV pelo questionário SF-36. RESULTADOS: O grupo CA apresentou menor distância percorrida no TC6min (metros) quando comparado com os grupos HBV e HCV (373,50±50,48; 464,16±32 e 475,94±27,84, respectivamente, p=0,001). Nos domínios do SF-36, o grupo CA apresentou menores escores na capacidade funcional e limitações por aspectos físicos quando comparado com os grupos HBV e HCV (p=0,001). Na comparação da força dos músculos respiratórios, o grupo CA apresentou menor PImáx (cmH2O) quando comparado com os grupos HBV e HCV (-65,54±11,28; -71,61±6,96; -82,44±13,71, respectivamente, p=0,001). A PEmáx (cmH2O) no grupo CA foi menor do que nos grupos HBV e HCV (65,13±10,74; 82,44±13,87; 83,44±12,20, respectivamente, p=0,001). CONCLUSÃO: O grupo CA demonstrou pior capacidade ao exercício, força muscular respiratória e QV quando comparado aos pacientes com HCV e HBV.

BACKGROUND: Liver diseases are responsible for metabolic disorders and loss of muscle mass and function that affect functional status and quality of life (QoL). OBJECTIVE: To compare exercise capacity, respiratory muscle strength, and QoL in liver transplant candidates with cirrhosis of the following etiologies: hepatitis C virus (HCV), hepatitis B virus (HBV), and alcoholic cirrhosis (AC). METHODS: Cross-sectional study comprising 86 patients divided into three groups: HCV (40 patients), HBV (14 patients), and AC (32 patients). Patients were evaluated using the Six-Minute Walk Test (6MWT), manometry, and the QoL questionnaire SF-36. RESULTS: The AC group showed the lowest performance in the 6MWT (meters) compared to the HBV and HCV groups (373.50±50.48, 464.16±32, and 475.94±27.84, respectively, p=0.001). In the domains of the SF-36, the AC group had lower scores for functional capacity and physical limitations when compared to the HBV and HCV groups (p=0.001). In the comparison of respiratory muscle strength, the AC group had lower MIP (cmH2O) compared to the HBV and HCV groups (-65.54±11.28, -71.61±6.96, -82.44±13.71, respectively, p=0.001). The MEP (cmH2O) in the AC group was also lower than in the HBV and HCV groups (65.13±10.74, 82.44±13.87, 83.44±12.20, respectively, p=0.001). CONCLUSION: The AC group showed worse exercise capacity, respiratory muscle strength, and QoL compared to patients with HCV and HBV.

Glutamine prevents gastric oxidative stress in an animal model of portal hypertension gastropathy.

BACKGROUND AND RATIONALE: Portal hypertension (PHI) is a clinical syndrome characterized by increases of the blood flow and/or of the vascular resistance in the portal system. A direct consequence of PHI can appearance different lesions on the gastric mucosa and submucosa, cumulatively termed portal hypertensive gastropathy (PHG). AIMS: To investigate the effects of glutamine on oxidative stress in an experimental model of PHG induced by partial portal vein ligation (PPVL). MATERIAL AND METHODS: Portal pressure, transaminase and alkaline phosphatase activity were quantified. Gastric tissue damage was assessed by histological analysis. Oxidative stress was measured by quantification of cytosolic concentration of thiobarbituric acid reactive substances (TBARS), hydroperoxide-initiated chemiluminescence (QL), and nitric oxide (NO) production. Moreover, activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were analyzed. RESULTS: Transaminase and alkaline phosphatase activities were not significantly modified by PPVL, indicating absence of liver injury. Histological analysis of gastric sections showed a lost of normal architecture, with edema and vasodilatation. TBARS, QL, and NO production were significantly increased in PPVL animals. A reduction of SOD activity was found. Glutamine administration markedly alleviated histological abnormalities and oxidative stress, normalized SOD activity, and blocked NO overproduction. CONCLUSIONS: Our results confirm that the use of molecules with antioxidant capacity can provide protection of the gastric tissue in portal hypertension. Glutamine treatment can be useful to reduce the oxidative damage induced by PHI on gastric tissue.

Endoscopic dilation of benign esophageal strictures without fluoroscopy: experience of 2750 procedures.

BACKGROUND/AIMS: To report a large series of patients with strictures from different etiologies who underwent dilation without fluoroscopy. METHODOLOGY: Between 1992 and 2005, 321 patients who underwent 2750 dilation sessions were entered in a database. Dysphagia score, cause and location of the stricture and diameter of the bougies were recorded in every session. RESULTS: The mean follow-up period was 18.8 months. Stricture was postsurgical in 204 patients, peptic in 60, caustic in 13, postradiotherapy in 13, and from other causes in 31. Clinical response was achieved in 92% of the postsurgical patients; 84% of the caustic injuries; 81% of the peptic patients; and 58% of the radiation injuries (p < 0.05). Absence of dysphagia was obtained in 68, 38, 67 and 27% of these, respectively (p < 0.05). All groups showed a significant improvement in dysphagia score, and 98% of patients in whom a 45F catheter was inserted, achieved clinical response. There were 6 perforations, with 2 deaths. CONCLUSIONS: Endoscopic dilation for benign esophageal strictures without fluoroscopy is safe and effective. Postsurgical patients show excellent results for dilation, and caustic and post-radiotherapy strictures have the worst response. A diameter of 45F is a satisfactory end-point for therapy in the majority of cases.

Diabetes mellitus and anal sphincter pressures: an experimental model in rats.

PURPOSE: Symptoms of the gastrointestinal tract, frequent in patients with diabetes mellitus, which may be related to an increase in the production of free radicals, include alterations in the function of the sphincter anal musculature. Such alterations are characterized by a decrease of muscular tone associated with different degrees of fecal incontinence. This study was performed to show the alterations in the anal sphincter pressures of diabetic rats and to evaluate the role of nitric oxide and oxidative stress in this situation. METHODS: Male Wistar rats weighing 250 to 400 g were used. The animals were divided in two groups: control and diabetic. Diabetes was induced through intraperitoneal injection of streptozotocin and the anal pressures were gauged by anorectal manometry. Nitric oxide was evaluated through measures of nitrites and nitrates, and oxidative stress through the technique of chemoluminescence. RESULTS: There was a significant decrease in the sphincter anal pressure of diabetic animals 60 days after induction (P < 0.05). This pressure returned to basal values after administration of a nitric oxide synthase antagonist. The levels of nitrites and nitrates as well as of lipoperoxidation were significantly increased in the diabetic compared with the control group (P < 0.05). CONCLUSIONS: In this study, hyperglycemia of diabetes mellitus caused an increase in the oxidative stress. Apparently the elevation of nitric oxide levels was one of the responsible factors for the decrease of anal sphincter pressures.

The efficacy of endoscopic ligation for the prevention of variceal rebleeding in cirrhotic patients according to the hepatocellular function.

BACKGROUND/AIMS: Endoscopic variceal ligation is considered the leading therapy for the prevention of variceal rebleeding in cirrhotic patients. However, the efficacy of this method in cirrhotic patients with poor hepatocellular function is not well-known yet. The aim of this study is to compare the efficacy of endoscopic variceal ligation for the eradication of esophageal varices, rebleeding and mortality rates, based on hepatocellular function, as graded by Child-Pugh. METHODOLOGY: Between June 1996 and December 2001, 163 consecutive cirrhotic patients were submitted to band ligation at our Department. Of these cases, 128 patients with previous variceal bleeding (mean age = 50.7 years; 90 males and 38 females) were followed-up. 55 patients were graded as Child A, 49 as Child B and 24 as Child C. RESULTS: The mean follow-up period for all groups was 17.3 months. Varices were eradicated in 82.7% (86 of 104 cases) of Child A/B cirrhotic patients and in 54.2% (13 of 24 cases) of Child C cases (p=0.0061). Eradication was achieved after a mean of 3.7 sessions, and no difference was observed among the groups. Varices recurred in 38.4% (38 of 99 cases) of the patients, presenting no difference among the different Child classes. However, there was a trend to a higher rebleeding rate among patients with variceal recurrence (21% vs. 8.2%, p=0.075). Rebleeding occurred in 20.2% (21 of 104 cases) of Child A/B cirrhotics and in 41.7% (10 of 24 cases) of Child C patients (p=0.001 log-rank test). The mortality rate was 13.5% (14 of 104 cases) among Child A/B patients and 37.5% (9 of 24 cases) among Child C cases (p=0.0135). CONCLUSIONS: Endoscopic variceal ligation is an effective method for the prevention of rebleeding in patients with better liver function. Child C patients had a poor response to treatment. These patients, in a statistically significant fashion, had a worse eradication rate and greater rebleeding and mortality rates than Child A/B patients.

Effects of quercetin on liver damage in rats with carbon tetrachloride-induced cirrhosis.

Flavonoids are reported to exhibit a wide variety of biological effects, including antioxidant and free radical-scavenging activities. Evidence of oxidative reactions is often associated with various chronic disease processes characterized by accumulation of connective tissue. This study was aimed to investigate the protective effects of chronic administration of the flavonoid quercetin (150 micromol/kg body wt/day intraperitoneally) in rats with carbon tetrachloride-induced fibrosis. In animals rendered cirrhotic by administration of carbon tetrachloride for 16 weeks, cell necrosis, fibrosis, and inflammatory infiltration were found. Histological abnormalities were accompanied by a higher hepatic content of collagen and thiobarbituric acid-reactive substances. Expression of inducible nitric oxide synthase (iNOS) was significantly increased in the liver. Treatment with quercetin during 3 weeks improved liver histology and reduced collagen content, iNOS expression, and lipid peroxidation. Those effects were associated with an increased total peroxyl radical-trapping antioxidant capacity of liver. We conclude that quercetin is effective in this model of liver damage.