Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selenium (Se) is a metalloid with chemical properties closed to those of sulfur, but they can not substitute for one another in vivo. Se body content reflected soil Se content (13 to 20 mg in North Americans, 3 to 6 in New Zealand residents). The daily intake recommended is 50 to 200 micrograms. In the diet Se occurs in mineral or organic forms, the bioavailability of these latter is better. Se as selenocysteine is incorporated in specific proteins such as glutathione peroxidase (GSH-Px). Se is metabolized in H2Se by reductive pathways. H2Se is methylated and methylated compounds are excreted in the urines. The Se urinary excretion represents the principal known process of Se regulation. Se bound to GSH-Px participates to free radical destruction and cellular membrane protection. Its role is complementary of vitamin E effect. Se also seems indispensable to appropriate immune response. It can chelate various metals allowing their detoxication. Se metabolism can be studied by Se assay in serum, whole blood, urine (reference values must be performed for each studied population) and by GSH-Px activity determination in erythrocytes or platelets. Vitamin E assay completes estimation of the antioxidative status of organism. Few Se intoxications have been recognized but Se deficiencies often happen. They can lead to a cardiomyopathy (Keshan disease), increase the risk of cardiovascular diseases or cancer. Se deficiencies are found in chronic renal failure, malnutrition malabsorption, long term parenteral nutrition. At the present time it is not known how Se deficiency interfers with chronic infections which often go with these diseases. A better knowledge of Se requirements and Se role could allow an appropriate supplementation in various diseases.
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PMID:[Selenium: physiologic role and value in human pathology]. 305 85

Oxygen free radicals have been implicated as mediators of tissue injury in a variety of diseases. We investigated the role of oxidative injury and oxygen free radical scavengers in liver cell injury associated with obstructive jaundice in Wistar rats. Bile duct ligation for 4 or 7 days led to a decrease in both vitamin E and A in the plasma and liver of male Wistar rats, indicating the malabsorption of lipid-soluble vitamins. Serum bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase activities were increased in the bile-duct-ligated rats. Furthermore, marked increases in lipid peroxide and oxidized glutathione levels indicated cholestatic liver injury. The antioxidant defense system was impaired, as shown by decreases in reduced glutathione and in the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase. Moreover, these high lipid peroxide levels and low levels of antioxidants correlated with the severity of jaundice. After releasing the bile duct ligation, levels of bilirubin, lipid peroxide and oxidized glutathione declined, while the levels of vitamin E and A, reduced glutathione, and the activities of GSH-Px increased, indicating an improvement in liver function. These findings suggest that lipid peroxidation is associated with the pathogenesis of liver damage in animals with bile duct ligation. Meanwhile, free oxygen radical scavengers are reduced in the bile-duct-ligated rats, thereby increasing the susceptibility of the liver to injury by oxygen-derived free radicals.
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PMID:Biochemical events associated with ligation of the common bile duct in Wistar rats. 903 77

The control of luminal thiol-disulfide redox state may be important for several intestinal functions, including absorption of iron or selenium and maintenance of mucus fluidity. Disulfides are present in the diet, and although luminal thiols are supplied in bile, little is known about the ability of the small intestine to reduce disulfides to maintain the luminal thiol-disulfide redox state. The objective of the current study was to determine whether the isolated, vascularly perfused jejunum, free from biliary thiols, could reduce intraluminal glutathione disulfide (GSSG) to glutathione (GSH). GSSG was introduced in a deoxygenated solution to inhibit the reoxidation of any GSH formed, and preparations were pretreated with acivicin to inhibit the degradation of GSH by gamma-glutamyltransferase. GSSG (250 micromol/L) was reduced to GSH, with the luminal redox potential (E(h)) for GSSG/2GSH changing from >0 to -111, -132 and -143 mV at 10, 20 and 30 min, respectively. The E(h) for luminal cystine/2cysteine was approximately 20 mV more reducing than that for GSSG/2GSH at each time point, suggesting that cysteine could function in the reduction of GSSG in the lumen. Measurements in specific regions showed that GSSG reduction was more rapid in the duodenum and proximal jejunum than in the distal jejunum. Preparations without acivicin treatment showed that E(h) values were unaffected by inhibition of gamma-glutamyltransferase despite differences in GSH and cysteine pool sizes. Rat intestine has a mechanism to adjust the luminal thiol-disulfide redox. In principle, dysfunction of this mechanism could contribute to malabsorption or other nutritional disorders.
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PMID:Rat jejunum controls luminal thiol-disulfide redox. 1105 15

The anti-tumour drug methotrexate (MTX) induces intestinal mucosa injury resulting in malabsorption and diarrhoea. The purpose of this study was to investigate whether exogenous melatonin could protect the gut from MTX-induced damage in rats. A single dose of MTX (20 mg kg(-1), i.p.) was followed by i.p. saline or melatonin injections (10 mg kg(-1), MTX + Mel) for the next 5 days. On the fifth day, intestinal transit was assessed using charcoal propagation. Rats were decapitated and small intestinal segments were fixed for light (LM) and scanning electron microscope (SEM) examinations. Other intestinal segments were stored to measure glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) and ATPase activity. MTX led to loss of more than 10% of the initial body weight (p < 0.01). Conversely, weight loss was markedly less in the melatonin-treated MTX group (p < 0.05). Bowel motility was increased in MTX-treated rats, while the transit index in the MTX-Mel group was not different from the control group. MTX caused decreases in GSH levels and ATPase activity, with increases in MDA levels and MPO activity. These changes were reversed in MTX-Mel-treated rats (p < 0.05-p < 0.001). LM and SEM in the MTX group revealed desquamation of surface epithelium and glandular degeneration, while the epithelium was slightly damaged in the MTX-Mel group. In conclusion, the present study demonstrates that melatonin is capable of reversing MTX-induced intestinal dysfunctions, indicating that it may be beneficial in ameliorating the symptoms of chemotherapy-induced enteritis.
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PMID:Amelioration of methotrexate-induced enteritis by melatonin in rats. 1512 82

Patients with chronic cholestasis, particularly those with associated cirrhosis, are susceptible to infectious complications. A predictable consequence of cholestasis is malabsorption of fat-soluble vitamins and free radical scavengers. On the other hand, it has been postulated that cholestasis affects polymorphonuclear leukocytes function by impeding chemotaxis, phagocytosis and superoxide anion release in experimental animals. This work is aimed to evaluate the antioxidant status and phagocytic activity of neutrophils in chronic liver disease patients. 15 primary biliary cirrhosis (PBC) patients, 15 primary sclerosing cholangitis (PSC) patients, 15 chronic viral hepatitis C (HCV) patients, and 15 healthy individuals (control group) were included in this study. Levels of catalase (Cat), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and malondialdehyde (MDA) were assessed in both serum and neutrophils homogenates. Neutrophils function was estimated by nitroblue tetrazolium (NBT) reduction assay. A marked decrease in the antioxidant status was observed in serum and neutrophils' homogenate of patients with chronic liver diseases compared to healthy subjects. Significant elevation of lipid peroxides was found in all groups of liver disease patients. The majority of patients had reduced value in NBT reduction assay, which suggested a lack of response to infection by neutrophils. In conclusion, deficient antioxidant defense mechanisms may lead to excess oxygen free radicals formation that promote the pathological process in the liver. The use of free radicals scavengers by chronic liver patients may potentiate the antioxidant defense system against oxidative stress.
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PMID:Study of antioxidant enzymes level and phagocytic activity in chronic liver disease patients. 1571 21

The intestinal mucosa is an important target of human immunodeficiency virus (HIV) infection. HIV virus induces CD4+ T cell loss and epithelial damage which results in increased intestinal permeability. The mechanisms involved in nutrient malabsorption and alterations of intestinal mucosal architecture are unknown. We previously demonstrated that HIV-1 transactivator factor (Tat) induces an enterotoxic effect on intestinal epithelial cells that could be responsible for HIV-associated diarrhea. Since oxidative stress is implicated in the pathogenesis and morbidity of HIV infection, we evaluated whether Tat induces apoptosis of human enterocytes through oxidative stress, and whether the antioxidant N-acetylcysteine (NAC) could prevent it. Caco-2 and HT29 cells or human intestinal mucosa specimens were exposed to Tat alone or combined with NAC. In an in-vitro cell model, Tat increased the generation of reactive oxygen species and decreased antioxidant defenses as judged by a reduction in catalase activity and a reduced (GSH)/oxidized (GSSG) glutathione ratio. Tat also induced cytochrome c release from mitochondria to cytosol, and caspase-3 activation. Rectal dialysis samples from HIV-infected patients were positive for the oxidative stress marker 8-hydroxy-2'-deoxyguanosine. GSH/GSSG imbalance and apoptosis occurred in jejunal specimens from HIV-positive patients at baseline and from HIV-negative specimens exposed to Tat. Experiments with neutralizing anti-Tat antibodies showed that these effects were direct and specific. Pre-treatment with NAC prevented Tat-induced apoptosis and restored the glutathione balance in both the in-vitro and the ex-vivo model. These findings indicate that oxidative stress is one of the mechanism involved in HIV-intestinal disease.
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PMID:The HIV-1 transactivator factor (Tat) induces enterocyte apoptosis through a redox-mediated mechanism. 2221 81

The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro- and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSH-related antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheral blood of children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.
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PMID:Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients. 2244 7

Celiac disease (CD) is a multifactorial, inflammatory small bowel disorder characterized by nutrient malabsorption resulting from mucosal damage, the latter induced by cereal products like barley, oat, and wheat. Oxidative stress has previously been reported to play an important role in the pathogenesis of CD. In the present study, we aimed to evaluate the frequency of polymorphisms that affects the structure of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), with levels being dependent on the amount of oxidative stress and whether or not there is an association with the mutations DQA1*0501, DQB1*0201, and DRB1*04 that are frequently reported for CD. SOD and GSH-Px polymorphisms were investigated by real-time quantitative polymerase chain reaction in 265 cases. Of the 117 cases that had at least one of DQA1*0501, DQB1*0201, or DRB1*04, 98 (83.75%) also had SOD enzyme polymorphisms and 68 (58.12%) also had GSH-Px polymorphisms. In conclusion, although the etiology of CD is not yet entirely clear, many mechanisms have been suggested. This study supports the notion that SOD and GSH-Px polymorphisms are involved in CD development, even though our findings were not statistically significant, and, furthermore, are influenced at various levels. SOD polymorphisms and activities were more frequently identified than those of GSH-Px.
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PMID:Evaluation of glutathione peroxidase and superoxide dismutase enzyme polymorphisms in celiac disease patients. 2463 24