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| 1 | Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy显示文摘AIM: To investigate the effects of glutamine on oxidative/nitrosative stress and the vascular endothelial growth factor (VEGF)-Akt-endothelial nitric oxide synthase (eNOS) signaling pathway in an experimental model of portal hypertension induced by partial portal vein ligation (PPVL). METHODS: Portal hypertension was induced by PPVL. The PPVL model consists of a partial obstruction of the portal vein, performed using a 20 G blunt needle as a guide, which is gently removed after the procedure. PPVL model was performed for 14 d beginning treatment with glutamine on the seventh day. On the fifteenth day, the mesenteric vein pressure was checked and the stomach was removed to test immunoreactivity and oxidative stress markers. We evaluated the expression and the immunoreactivity of proteins involved in the VEGF-Akt-eNOS pathway by Western blotting and immunohistochemical analysis. Oxidative stress was measured by quantification of the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) as well as the levels of total glutathione (GSH), superoxide dismutase (SOD) activity, nitric oxide (NO) production and nitrotyrosine immunoreactivity. RESULTS: All data are presented as the mean ± SE. The production of TBARS and NO was significantly increased in PPVL animals. A reduction of SOD activity was detected in PPVL + G group. In the immunohistochemical analyses of nitrotyrosine, Akt and eNOS, the PPVL group exhibited significant increases, whereas decreases were observed in the PPVL + G group, but no difference in VEGF was detected between these groups. Western blotting analysis detected increased expression of phosphatidylinositol-3-kinase (PI3K), P-Akt and eNOS in the PPVL group compared with the PPVL + G group, which was not observed for the expression of VEGF when comparing these groups. Glutamine administration markedly alleviated oxidative/nitrosative stress, normalized SOD activity, increased levels of total GSH and blocked NO overproduction as well as the formation of peroxynitrite. CONCLUSION: Glutamine treatment demonstrated to reduce oxidative damage but does not reduce angiogenesis induced by PH in gastric tissue, demonstrating a beneficial role for the PI3K-Akt-eNOS pathway. | Camila Marques Francielli Licks Ingrid Zattoni Beatriz Borges Luiz Eduardo Rizzo de Souza Claudio Augusto Marroni Norma Possa Marroni | 2013 | World Journal of Gastroenterology2013，19，28： | 9 |
| 2 | Liver transplantation and alcoholic liver disease:History,controversies,and considerations显示文摘Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease(ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation(LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a 'self-inflicted disease'. One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this '6-mo rule' is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy. | Claudio Augusto Marroni Alfeu de Medeiros Fleck Jr Sabrina Alves Fernandes Lucas Homercher Galant Marcos Mucenic Mario Henrique de Mattos Meine Guilherme Mariante-Neto Ajacio Bandeira de Mello Brandao | 2018 | World Journal of Gastroenterology2018，24，26： | 7 |
| 3 | Glutamine prevents oxidative stress in a model of mesenteric ischemia and reperfusion显示文摘AIM: To evaluate preventative effects of glutamine in an animal model of gut ischemia/reperfusion(I/R).METHODS: Male Wistar rats were housed in a controlled environment and allowed access to food and water ad libitum. Twenty male Wistar rats were divided into four experimental groups:(1) control group(control)- rats underwent exploratory laparotomy;(2) control + glutamine group(control-GLU)- rats were subjected to laparotomy and treated intraperitoneally with glutamine 24 and 48 h prior to surgery;(3) I/R group- rats were subjected to occlusion of the superior mesenteric artery for 30 min followed by 15 min of reperfusion; and(4) ischemia/reperfusion + glutamine group(G + I/R)- rats were treated intraperitoneally with glutamine 24 and 48 h before I/R. Local and systemic injuries were determined by evaluating intestinal and lung segments for oxidative stress using lipid peroxidation and the activity of superoxide dismutase(SOD), interleukin-6(IL-6) and nuclear factor kappa beta(NFkB) after mesenteric I/R. RESULTS: Lipid peroxidation of the membrane was increased in the animals subjected to I/R(P < 0.05). However, the group that received glutamine 24 and 48 h before the I/R procedure showed levels of lipid peroxidation similar to the control groups(P < 0.05). The activity of the antioxidant enzyme SOD was decreased in the gut of animals subjected to I/R when compared with the control group of animals not subjected to I/R(P < 0.05). However, the group that received glutamine 24 and 48 h before I/R showed similar SOD activity to both control groups not subjected to I/R(P < 0.05). The mean area of NF-kB staining for each of the control groups was similar. The I/R group showed the largest area of staining for NF-kB. The G + I/R group had the second highest amount of staining, but the mean value was much lower than that of the I/R group(P < 0.05). For IL-6, control and control-GLU groups showed similar areas of staining. The I/R group contained the largest area of IL-6 staining, followed by the G + I/R animals; however, this area was significantly lower than that of the group that underwent I/R without glutamine(P < 0.05). CONCLUSION: These results demonstrate that pretreatment with glutamine prevents mucosal injury and improves gut and lung recovery after I/R injury in rats. | Gilmara Pandolfo Zabot Gustavo Franco Carvalhal Norma Possa Marroni Renata Minuzzo Hartmann Vinícius Duval da Silva Henrique Sarubbi Fillmann | 2014 | World Journal of Gastroenterology2014，20，32： | 7 |
| 4 | Nutritional evaluation in cirrhosis: Emphasis on the phase angle显示文摘Protein-calorie malnutrition(PCM) is a common condition in cirrhotic patients, leading to a worse prognosis, complications, poor quality of life and lower survival rates. Among ways of assessing nutritional status, there are anthropometric methods such as the evaluation of the triceps skinfold, the arm circumference, the arm muscle circumference and the body mass index, and nonanthropometric methods such as the subjective global assessment, the handgrip strength of non-dominant hand, and the bioelectrical impedance analysis(BIA). PCM is frequently under-diagnosed in clinical settings in patients with cirrhosis due to the limitations of nutritional evaluation methods in this population. BIA is a useful method, but cannot be indicated in patients with abnormal body composition. In these situations, the phase angle(PA) has been used, and can become an important tool in assessing nutritional status in any situation. The PA is superior to anthropometric methods and might be considered as a nutritional indicator in cirrhosis. The early characterization of the nutritional status in patients with cirrhosis means an early nutritional intervention, with a positive impact on patients' overall prognosis. Among the usually accepted methods for nutritional diagnosis, the PA provides information in a quick and objective manner. | Sabrina Alves Fernandes Angelo Alves de Mattos Cristiane Valle Tovo Claudio Augusto Marroni | 2016 | World Journal of Hepatology2016，8，29： | 6 |
| 5 | Protective action of glutamine in rats with severe acute liver failure显示文摘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 NFκBmediated 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 inflammatoryinfiltration, 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-1β, 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 NO_2 and NO_3 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. | Elizangela G Schemitt Renata M Hartmann Josieli R Colares Francielli Licks Jéferson O Salvi Cláudio A Marroni Norma P Marroni | 2019 | World Journal of Hepatology2019，11，3： | 5 |
| 6 | Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation显示文摘AIM To evaluate the effects of melatonin(Mel) on oxidative stress in an experimental model of bile duct ligation(BDL).METHODS Male Wistar rats(n = 32, weight ± 300 g) were allocated across four groups: CO(sham BDL), BDL(BDL surgery), CO + Mel(sham BDL and Mel administration) and BDL + Mel(BDL surgery and Mel administration). Mel was administered intraperitoneally for 2 wk, starting on postoperative day 15, at a dose of 20 mg/kg.RESULTS Mel was effective at the different standards, reestablishing normal liver enzyme levels, reducing the hepatosomatic and splenosomatic indices, restoring lipoperoxidation and antioxidant enzyme concentrations, reducing fibrosis and inflammation, and thereby reducing liver tissue injury in the treated animals.CONCLUSION The results of this study suggest a protective effect of Mel when administered to rats with secondary biliary cirrhosis induced by BDL. | Josieli Raskopf Colares Elizângela Goncalves Schemitt Renata Minuzzo Hartmann Francielli Licks Mariana do Couto Soares Adriane Dal Bosco Norma Possa Marroni | 2016 | World Journal of Gastroenterology2016，22，40： | 3 |
| 7 | Glutamine prevents oxidative stress in a model of portal hypertension显示文摘AIM To evaluate the protective effects of glutamine in a model of portal hypertension(PH) induced by partial portal vein ligation(PPVL).METHODS Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum. Twenty-four male Wistar rats were divided into four experimental groups:(1) control group(SO)-rats underwent exploratory laparotomy;(2) control + glutamine group(SO + G)-rats were subjected to laparotomy and were treated intraperitoneally with glutamine;(3) portal hypertension group(PPVL)-rats were subjected to PPVL; and(4) PPVL + glutamine group(PPVL + G)-rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase(GPx), endothelial nitric oxide synthase(e NOS) and inducible nitric oxide synthase(i NOS) after PPVL.RESULTS Lipid peroxidation of the membrane was increased in the animals subjected to PH(P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups(P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH(P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH(P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification(44 pixel = 1 μm) were captured. The sum means of all áreas, of each group were calculated. The mean areas of e NOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for e NOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group(P < 0.01). For i NOS, the control(SO) and control + G(SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of i NOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine(P < 0.01).CONCLUSION Treatment with glutamine prevents gut mucosal injury after PH in rats. | Gilmara Pandolfo Zabot Gustavo Franco Carvalhal Norma Possa Marroni Francielli Licks Renata Minuzzo Hartmann Vinícius Duval da Silva Henrique Sarubbi Fillmann | 2017 | World Journal of Gastroenterology2017，23，25： | 3 |
| 8 | N-acetylcysteine modulates angiogenesis and vasodilation in stomach such as DNA damage in blood of portal hypertensive rats显示文摘AIM: To evaluate the antioxidant effect of N-acetylcysteine(NAC) on the stomach of rats with portal hypertension.METHODS: Twenty-four male Wistar rats weighing ± 250 g were divided into four experimental groups(n =6 each): Sham-operated(SO),SO + NAC,partial portal vein ligation(PPVL),and PPVL + NAC. Treatment with NAC in a dose of 10 mg/kg(i.p.) diluted in 0.6 m L of saline solution was administered daily for 7 d starting 8 d after the surgery. Animals from the PPVL and SO group received saline solution(0.6 m L) for the same period of time as the PPVL + NAC and SO + NAC group. On the 15 th day the animals were anesthetized and we evaluated portal pressure by cannulating mesenteric artery. After,we removed the stomach for further analysis. We performed immunohistochemical analysis for endothelial nitric oxide synthase(e NOS),vascular endothelial growth factor(VEGF),and nitrotirosine(NTT) proteins in stomach. We also evaluated e NOS and VEGF by Western blot analysis and assessed DNA damage in blood samples by the comet assay.RESULTS: The portal hypertension group exhibited increases in portal pressure when compared to SO group(29.8 ± 1.8 vs 12.0 ± 0.3 mm Hg)(P < 0.001). The same was observed when we compared the e NOS(56.8 ± 3.7 vs 13.46 ± 2.8 pixels)(P < 0.001),VEGF(34.9 ± 4.7 vs 17.46 ± 2.6 pixels)(P < 0.05),and NTT(39.01 ± 4.0 vs 12.77 ± 2.3 pixels)(P < 0.05) expression by immunohistochemistry of the PPVL animals with the SO group. The expression of e NOS(0.39 ± 0.03 vs 0.25 ± 0.03 a.μ)(P < 0.01) and VEGF(0.38 ± 0.04 vs 0.26 ± 0.04 a.μ)(P < 0.01) were also evaluated by Western blot analysis,and we observed an increase of both proteins on PPVL animals. We also evaluated the DNA damage by comet assay,and observed an increase on damage index and damage frequency on those animals. NAC decreased portal pressure values in PPVL + NAC animals(16.46 ± 2 vs 29.8 ± 1.8 mm Hg)(P < 0.001) when compared to PPVL. The expression of e NOS(14.60 ± 4.1 vs 56.8 ± 3.7 pixels)(P < 0.001),VEGF(19.53 ± 3.2 vs 34.9 ± 4.7 pixels)(P < 0.05) and NTT(21.84 ± 0.7 vs 39.01 ± 4.0 pixels)(P < 0.05) evaluated by immunohistochemistry were also reduced in PPVL + NAC animals. Also,when evaluated by Western blot e NOS expression(0.32 ± 0.03 vs 0.39 ± 0.03 a.μ)(P < 0.05) and VEGF expression(0.31 ± 0.09 vs 0.38 ± 0.04 a.μ)(P < 0.01). Furthermore,NAC modulated DNA damage in PPVL + NAC animals.CONCLUSION: In view of these results,we believe NAC is able to protect the stomach from the alterations induced by the PPVL procedure. | Francielli Licks Renata Minuzzo Hartmann Camila Marques Elizangela Schemitt Josieli Raskopf Colares Mariana do Couto Soares Juliana Reys Camila Fisher Juliana da Silva Norma Possa Marroni | 2015 | World Journal of Gastroenterology2015，21，43： | 2 |
| 9 | Inhibition of Rat Testicular Nuclear Kinesins (krp2; KIFC5A) by Acrylamide as a Basis for Establishing a Genotoxicity Threshold 显示文摘 | Friedman MA Zeiger E Marroni DE | 2008 | Food Chem2008，56，15： | 1 |
| 10 | Overexpression of multiple drug resistance genes in endothelial cells from patients withrefractory epilepsy显示文摘 | Dombrowski SM Desai SY Marroni M | 2001 | Epilepsia2001，42，12： | 1 |
| 11 | Prognostic role of serum sialyl Lewisx (CD15s) in colorectal cancer显示文摘 | Paganuzzi M Bobbio B Marroni P | 2003 | Oncology2003，65，1： | 1 |
| 12 | Relationship between multiple drug resistance protein and p53 tumor suppressor gene proteins in human brain astrocytrs显示文摘 | Marroni M Agrawal ML Kight K | 2003 | Neuroscience2003，121，3： | 1 |
| 13 | Impact of cytomegalovirus infection on long-term survival after orthotopic liver transplantation显示文摘 | Hoppe L Marroni C A Bressane R | 2006 | Transplant Proc2006，38，： | 1 |
| 14 | Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy显示文摘 | Dombrowski SM Desai SY Marroni M | 2001 | Epilepsia2001，42，12： | 1 |
| 15 | Functional defect of natu- ral immune system in an apparent immunoeompetent patient with pulmonary cryptococcosis显示文摘 | Marroni M Pericolini E Conci E | 2007 | J Infect2007，54，5： | 1 |
| 16 | D-MELD does not predict post-liver transplantation survival:a single-center experience from Brazil显示文摘 | Costabeber AM Liono LC Marroni C | 2014 | Ann Hepatol2014，13，6： | 1 |
| 17 | Consistent interethnic differences in the distribution of clinically relevant endothelial nitric oxide synthase genetic polymorphisms显示文摘 | Marroni AS Metzger IF Souza-Costa DC | 2005 | Nitric Oxide2005，12，3： | 1 |
| 18 | Durability Study and Life-time Prediction of Baseline Proton Exchange Membrane Fuel CellUnder Severe Operating Conditions显示文摘 | Marrony M Barrera R Quenet S | 2008 | Journal of Power Sources2008，182，2： | 1 |
| 19 | Quercetin prevents oxidative stress and NF-κB activation in gastric mucosa of portal hypertensive rats显示文摘 | Andrea J. Moreira Christina Fraga María Alonso Pilar S. Collado Claudio Zetller Claudio Marroni Norma Marroni Javier González-Gallego | 2004 | Biochemical Pharmacology2004，，10： | 1 |
| 20 | Prognostic role of serum sialyl Lewisx (CD15s) in colorectal cancer显示文摘 | Paganuzzi M Bobbio B Marroni P | 2003 | Oncology2003，65，1： | 1 |
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