Copper-Zinc ratio and nutritional status in colorectal cancer patients during the perioperative period.

PURPOSE: This study aimed to determine Cu/Zn ratio, nutritional and inflammatory status in patients during the perioperative period for colorectal cancer. METHODS: The study included patients with histological diagnosis of colorectal adenocarcinoma (Cancer Group, n=46) and healthy volunteers (Control Group, n=28). We determined habitual food intake, body composition, laboratory data of nutritional status, serum calprotectin and plasma Cu and Zn concentrations. Mann-Whitney U-test was performed between-group comparisons and Spearman correlation test for correlations between the variables. RESULTS: Individuals in the Cancer Group presented significantly lower BMI, fat mass, plasma hemoglobin, total protein and albumin as compared with the Control Group. Serum calprotectin[70.1 ng/mL (CI95% 55.8-84.5) vs.53.3 ng/mL (40.3-66.4), p=0.05], plasma Cu concentrations [120 µg/dL(CI95% 114-126) vs. 106 µg/dL(CI95% 98-114), p<0.01] and the Cu/Zn ratio [1.59 (CI95% 1.48-1.71)vs. 1.35 (CI95% 1.23-1.46), p=0.01]were higher in patients with colorectal cancer than in controls. Additionally, the Cancer Group showed negative correlations between the Cu/Zn ratio and Zn intake, hemoglobin, serum albumin, and positive correlation between the Cu/Zn ratio and serum calprotectin. CONCLUSION: These results indicate that an increased plasma Cu/Zn ratio and serum calprotectin, and decreased protein values may be a result of the systemic inflammatory response to the tumor process.

Effect of Zinc Supplementation on Antioxidant Defenses and Oxidative Stress Markers in Patients Undergoing Chemotherapy for Colorectal Cancer: a Placebo-Controlled, Prospective Randomized Trial.

The study aimed to investigate the effect of oral zinc supplementation on antioxidant defenses and oxidative stress markers during chemotherapy for colorectal cancer. Twenty-four patients who had undergone surgical resection of colorectal cancer participated in this placebo-controlled, prospective randomized study. The supplementation was started in the perioperative period, in which 10 patients received 70 mg of zinc (zinc group, n = 10) and 14 patients received placebo (placebo group, n = 14) for 16 weeks. Approximately 45 days after surgical resection of tumor, all patients received a chemotherapeutic regimen (capecitabine, capecitabine combined with oxaliplatin or 5-fluorouracil). Vitamin C, vitamin E, antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and lipid peroxidation markers malondialdehyde (MDA) and 8-isoprostane were determined before the first, second, third, and fourth chemotherapy cycles. Compared with the placebo group, the zinc group presented higher SOD values before the first, second, and fourth chemotherapy cycles and lower GPx values before the third cycle. There were no statistical differences between the study groups in vitamin C, vitamin E, MDA, or 8-isoprostane plasma values. Longitudinal analysis revealed decreased vitamin E concentration in the placebo group before the second and fourth cycles as compared with the initial values. Zinc supplementation during chemotherapy cycles increased SOD activity and maintained vitamin E concentrations. Although no effect of zinc supplementation on oxidative stress markers was observed, the increase in SOD activity indicates a production of stable free radicals, which may have a positive effect in cancer treatment.

Copper-Zinc ratio and nutritional status in colorectal cancer patients during the perioperative period

PURPOSE : This study aimed to determine Cu/Zn ratio, nutritional and inflammatory status in patients during the perioperative period for colorectal cancer. METHODS: The study included patients with histological diagnosis of colorectal adenocarcinoma (Cancer Group, n=46) and healthy volunteers (Control Group, n=28). We determined habitual food intake, body composition, laboratory data of nutritional status, serum calprotectin and plasma Cu and Zn concentrations. Mann-Whitney U-test was performed between-group comparisons and Spearman correlation test for correlations between the variables. RESULTS: Individuals in the Cancer Group presented significantly lower BMI, fat mass, plasma hemoglobin, total protein and albumin as compared with the Control Group. Serum calprotectin[70.1 ng/mL (CI95% 55.8-84.5) vs.53.3 ng/mL (40.3-66.4), p=0.05], plasma Cu concentrations [120 µg/dL(CI95% 114-126) vs. 106 µg/dL(CI95% 98-114), p<0.01] and the Cu/Zn ratio [1.59 (CI95% 1.48-1.71)vs. 1.35 (CI95% 1.23-1.46), p=0.01]were higher in patients with colorectal cancer than in controls. Additionally, the Cancer Group showed negative correlations between the Cu/Zn ratio and Zn intake, hemoglobin, serum albumin, and positive correlation between the Cu/Zn ratio and serum calprotectin. CONCLUSION: These results indicate that an increased plasma Cu/Zn ratio and serum calprotectin, and decreased protein values may be a result of the systemic inflammatory response to the tumor process.

INFLUENCE OF OXIDATIVE STRESS AND OBESITY IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS.

BACKGROUND: Nonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism. OBJECTIVE: Considering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology. METHODS: Fifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor. RESULTS: Nonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals. CONCLUSION: This paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.

INFLUENCE OF OXIDATIVE STRESS AND OBESITY IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS / Influência do estresse oxidativo e obesidade em pacientes com esteatohepatite não alcoólica

BackgroundNonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism.ObjectiveConsidering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology.MethodsFifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor.ResultsNonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals.ConclusionThis paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.

ContextoEsteatohepatite não alcoólica é considerada uma manifestação hepática da síndrome metabólica e está particularmente associada com a resistência insulínica, hipertensão, obesidade, anormalidades no metabolismo lipídico e da glicose.ObjetivoConsiderando a importância da obesidade e do estresse oxidativo na fisiopatogenia da esteatohepatite não alcoólica, o objetivo deste estudo foi avaliar a associação e presença da obesidade e do estresse oxidativo nesta patologia.MétodosQuinze pacientes com esteatohepatite não alcoólica (grupo esteatohepatite não alcoólica), diagnosticados de acordo com os achados histopatológicos da biópsia hepática, e 15 indivíduos sem esteatohepatite não alcoólica com sobrepeso/obesidade (grupo sem esteatohepatite não alcoólica) foram incluídos. Todos os voluntários eram acompanhados em Hospital Universitário Brasileiro. Avaliação nutricional (peso, altura, índice de massa corporal e circunferência abdominal) e bioquímica (glicemia de jejum, enzimas hepáticas, lipidograma, leptina, superóxido dismutase, glutationa peroxidase, vitaminas C e E, catalase e 8-isoprostano) foram realizadas em todos os indivíduos. O teste t de Student foi usado para análise estatística considerando o P≤0,05 como significativo.ResultadosIndivíduos do Grupo esteatohepatite não alcoólica apresentaram valores significativamente maiores de glicemia, AST, ALT, Gama GT, fosfatase alcalina, triglicérides e superóxido dismutase e menor valor de glutationa peroxidase, quando comparados ao Grupo sem esteatohepatite não alcoólica.ConclusãoEste artigo demonstra que somente a presença da obesidade não é suficiente para provocar alterações nos biomarcadores estudados. Apesar da maioria dos marcadores de estresse oxidativo apresentarem-se similar nas duas condições, os pacientes com esteatohepatite não alcoólica podem apresentar-se levemente mais afetados que os indivíduos sem esteatohepatite não alcoólica.

Methylenetetrahydrofolate reductase gene polymorphism and serum homocysteine levels in nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by hepatic fat accumulation in the absence of alcohol consumption. Hyperhomocysteinemia is considered an independent risk factor for liver diseases, and the genetic polymorphisms C677T and A1298C in the MTHFR gene have been linked to hyperhomocysteinemia. The purpose of this study was to investigate serum homocysteine (Hcy) concentrations and the MTHFR C677T and A1298C polymorphisms as risk factors for the development of NAFLD. METHODS: One hundred and thirty-four Brazilian patients with biopsy-proven NAFLD and 134 healthy controls were recruited. The MTHFR C677T and A1298C polymorphisms were detected through polymerase chain reaction restriction fragment length polymorphism. Serum Hcy levels were determined by chemiluminescence. RESULTS: Serum Hcy levels were higher in NAFLD patients as compared to control subjects, but there were no differences between patients with steatosis and nonalcoholic steatohepatitis. The NAFLD and control groups did not differ in genotypic and allelic frequencies of the MTHFR C677T and A1298C polymorphisms, either. Elevated plasma Hcy levels were positively correlated with age in the NAFLD subjects. CONCLUSION: The MTHFR C677T and A1298C polymorphisms are not genetic risk factors for the development of NAFLD. Higher Hcy levels exist in NAFLD subjects, but they are not associated with liver disease severity.

Peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms in nonalcoholic fatty liver disease: a study in Brazilian patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of hepatic steatosis in the absence of excess alcohol consumption. The pathogenesis of fatty liver disease and steatohepatitis (NASH) is not fully elucidated, but the common association with visceral obesity, hyperlipidemia, hypertension and type 2 diabetes mellitus (T2DM) suggests that it is the hepatic manifestation of metabolic syndrome. Peroxisome proliferator-activated receptor PPARα and PPARγ are members of a family of nuclear receptors involved in the metabolism of lipids and carbohydrates, adipogenesis and sensitivity to insulin. The objective of this study was to analyze the polymorphisms Leu162Val of PPARα and Pro12Ala of PPARγ as genetic risk factors for the development and progression of NAFLD. METHODS: One hundred and three NAFLD patients (89 NASH, 14 pure steatosis) and 103 healthy volunteers were included. Single nucleotide polymorphisms (SNPs) Leu162Val and Pro12Ala were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: NASH patients presented higher BMI, AST and prevalence of T2DM than patients with pure steatosis. A higher prevalence of 12Ala allele was observed in the NASH Subgroup when compared to Control Group. When we grouped NASH and Steatosis Subgroups (NAFLD), we found lower serum glucose and more advanced fibrosis in the Leu162Val SNP. On the other hand, there was no statistical difference in clinical, laboratorial and histological parameters according to the Pro12Ala SNP. CONCLUSIONS: We documented a lower prevalence of 12Ala allele of gene PPARγ in the NASH Subgroup when compared to Control Group. In NAFLD patients, there were no associations among the occurrence of Pro12Ala SNP with clinical, laboratorial and histological parameters. We also documented more advanced fibrosis in the Leu162Val SNP. The obtained data suggest that Pro12Ala SNP may result in protection against liver injury and that Leu162Val SNP may be involved in the progression of NAFLD.

Effect of methionine load on homocysteine levels, lipid peroxidation and DNA damage in rats receiving ethanol / Efeito da carga de metionina nos níveis de homocisteína, peroxidação lipídica e dano ao DNA em ratos que receberam etanol

Changes in the metabolism of methionine can cause hyperhomocysteinemia, inducing a triad of atherosclerosis, hypertension, and increased oxidative stress. The generation of free radicals and oxidative damage to DNA is important in the liver damage caused by ethanol. In this study, the effect of methionine overload associated or otherwise with acute administration of ethanol on homocysteine values, damage to DNA, lipoperoxidation and vitamin E was evaluated. Thirty rats were divided into 3 groups: Group Ethanol 24 hours (EG24), Group Methionine 24 hours (MG24), and Group Methionine and Ethanol 24 hours (MEG24). TBARS, vitamin E, GS and, homocysteine values were determined and the Comet assay was carried out. Increased GSH, vitamin E and homocysteine levels were observed for MEG24, and increased TBARS were observed in EG24. The Comet assay showed an increase in DNA damage in EG24 and DNA protection in MEG24. The administration of ethanol decreased antioxidant levels and increased TBARS, indicating the occurrence of oxidative stress with possible DNA damage. The combination of methionine and ethanol had a protective effect against the ethanol-induced damage, but increased the levels of homocysteine.

Alterações no metabolismo da metionina podem ocasionar hiper-homocisteinemia, quadro indutivo de aterosclerose, hipertensão e aumento do estresse oxidativo. A geração de radicais livres e dano oxidativo ao DNA são importantes na injúria hepática provocada pelo etanol. Neste estudo avaliaram-se os efeitos da sobrecarga de metionina associada ou não à administração aguda de etanol sobre valores de homocisteína, dano ao DNA, lipoperoxidação e vitamina E. Foram utilizados 30 ratos Wistar distribuídos em 3 Grupos: Grupo Etanol 24 horas (GE24), Grupo Metionina 24 horas (GM24) e Grupo Metionina e Etanol 24 horas (GME24). Realizaram-se determinações hepáticas de SRATB, vitamina E, GSH, homocisteína e Teste do Cometa e determinações plasmáticas de GSH e homocisteína. Valores aumentados de GSH, vitamina E e homocisteína foram observados para o GME24, e de SRATB no GE24. O Teste do Cometa mostrou aumento do dano ao DNA no GE24 e proteção ao DNA no GME24. A administração de etanol diminuiu os níveis de antioxidantes e aumentou o de SRATB, indicando ocorrência de estresse oxidativo, podendo ocasionar dano ao DNA. A presença da metionina associada com o etanol agiu como protetora contra os danos do etanol, mas aumentou os níveis de homocisteína.

Progression of lipid peroxidation measured as thiobarbituric acid reactive substances, damage to DNA and histopathological changes in the liver of rats subjected to a methionine-choline-deficient diet.

Methionine-choline-deficient diet represents a model for the study of the pathogenesis of steatohepatitis. Male rats were divided into three groups, the first group receiving a control diet and the other two groups receiving a methionine-choline-deficient diet for 1 month (MCD1) and for 2 months (MCD2), respectively. The livers of the animals were collected for the determination of vitamin E, thiobarbituric acid reactive substances (TBARS), GSH concentration, DNA damages, and for histopathological evaluation. The hepatic TBARS and GSH content was higher (P < 0.05) in the groups receiving the experimental diet (MCD1 and MCD2) compared to control diet, and hepatic vitamin E concentration differed (P < 0.05) between the MCD1 and MCD2 groups, with the MCD2 group presenting a lower concentration. Damage to hepatocyte DNA was greater (P < 0.05) in the MCD2 group (262.80 DNA injuries/100 hepatocytes) compared to MCD1 (136.4 DNA injuries/100 hepatocytes) and control diet (115.83 DNA injuries/100 hepatocytes). Liver histopathological evaluation showed that steatosis, present in experimental groups was micro- and macro-vesicular and concentrated around the centrolobular vein, zone 3, with preservation of the portal space. The inflammatory infiltrate was predominantly periductal and the steatosis and inflammatory infiltrate was similar in the MCD1 and MCD2 groups, although the presence of Mallory bodies was greater in the MCD2 group. The study describes the contribution of a methionine-choline-deficient diet to the progression of steatosis, lipid peroxidation and hepatic DNA damage in rats, serving as a point of reflection about the role of these nutrients in the western diet and the elevated non-alcoholic steatohepatitis rates in humans.

Hyperhomocysteinemia and polymorphisms of the methylenetetrahydrofolate gene in hemodialysis and peritoneal dialysis patients.

Hyperhomocysteinemia has been documented in chronic renal failure (CRF). Premature as well as progressive occlusive vascular disease is common. Mutations or polymorphisms in the gene of the enzyme methylenetetrahydrofolate reductase (MTHFR), as C677T, A1298C and G1793A, are associated with hyperhomocysteinemia and possibly with elevated risk for vascular diseases. This study was conducted on 89 individuals with renal failure on dialysis to determine the allelic and genotypic frequencies of the mutations in the MTHFR gene and hyperhomocysteinemia. Blood samples were colleted for determination of homocysteine and DNA. The C677T, A1298C and G1793A mutations were detected. This study confirmed the high prevalence of hyperhomocysteinemia in patients on dialysis, which was diagnosed in 76 patients (85.39%) and high incidence of the C677T and A1298C mutation, 42 (47.19%) and 29 (32.58%) patients, respectively. Five patients (5.62%) presented the G1793A mutation and hyperhomocysteinemia. The authors concluded that there was no influence of the polymorphisms on homocysteine levels in these patients.

DNA oxidative damage in patients with dialysis treatment.

BACKGROUND/AIMS: Chronic renal patients on hemodialysis (HD) and peritoneal dialysis (PD) treatment are exposed to oxidative stress and DNA damage. The objective of this study was to assess the oxidative damage to DNA in end-stage chronic renal failure, before and after vitamin E supplementation. METHODS: Patients on HD (n=29) and PD (n=22) received oral supplementation with 300 mg vitamin E three times a week for 4 weeks. A blood sample was collected at the beginning and at the end of the supplementation cycle for the determination of vitamin E levels (high-performance liquid chromatography), carbonyl groups, and DNA damage (8-hydroxy 2'-deoxyguanosine [8-OHdG] and comet assay). RESULTS: After supplementation, vitamin E concentration was increased by about 50%. Protein oxidation was initially observed in both groups, with a reduction after supplementation. DNA damage detected by the comet assay and by 8-OHdG analysis was significantly reduced (p<0.05) after supplementation in both groups. CONCLUSIONS: Vitamin E supplementation reduced oxidative DNA damage in both HD and PD patients. Treatments such as HD and PD induce oxidative stress and consequent DNA damage, and increased plasma vitamin E levels significantly contribute to the normalization of these events.