Glutathione level and glutathione-dependent enzyme activities in blood serum of patients with gastrointestinal tract tumors.

OBJECTIVES: Glutathione (GSH) and enzymes cooperating with it - glutathione peroxidase (GSHPx), glutathione S-transferase (GST) and glutathione reductase (GSHR) - play crucial role in cell defence against reactive oxygen species (ROS), which are implicated in tumor disease. The aim of this study was to determine if neoplastic diseases of gastrointestinal tract may influence blood GSH level and its dependent enzyme activity. DESIGN AND METHODS: Blood serum was obtained before and after surgery from patients with gastric, liver and colorectal cancers, and colorectal cancer liver metastases. Lipid peroxidation and GSH levels, and GSH-dependent enzyme activities were determined by means of spectrophotometric methods. RESULTS: Increased level of lipid peroxidation and significant differences in GSH level and GSHPx, GST and GSHR activities were observed in serum taken before and after surgery from patients with gastrointestinal tract tumors compared to those in control serum (from healthy blood donors). CONCLUSIONS: Increase of lipid peroxidation and changes in GSH level and related enzyme activities, suggest oxidative stress in serum of patients with gastrointestinal tract tumor causes, which probably arise as a result of enormous production of ROS in the system. These alterations reflect the presence of functional defence mechanism against oxidative stress related firmly to the glutathione metabolism.

Activity and protein level of CuZnSOD and MnSOD in benign and malignant liver tumors.

OBJECTIVES: Superoxide dismutase (SOD) is a key antioxidant enzyme, responsible for scavenging of superoxide anion - a precursor of all reactive oxygen species (ROS). ROS are implicated in many pathologies, particularly in tumor disease. The aim of our work was to evaluate SOD isoforms' activity and protein level changes in liver tumors. DESIGN AND METHODS: Materials were obtained from patients with liver tumors and with liver cirrhosis diagnosed by routine histopathological examination. Activity and protein level of SOD were determined by means of the Beauchamp and Fridovich assay and by Western blot analysis. RESULTS: Decreased activity of CuZnSOD and MnSOD and distinct differences in SOD isoforms' protein expression in liver cirrhosis were found. Results also showed higher protein level and activity of SOD isoforms in liver malignant tumors than in benign ones. CONCLUSIONS: Malignant tumors have a better antioxidant system than benign ones. Moreover, weakening of antioxidant mechanisms and accumulation of oxidative damage in cirrhotic liver could initiate liver carcinogenesis.

[Catalase: structure, properties, functions]. / Katalaza--budowa, wlasciwosci, funkcje.

Catalase (EC 1.11.1.6) is an enzyme which is present mainly in the peroxisomes of mammalian cells. It is a tetrameric enzyme consisting of four identical, tetrahedrally arranged subunits of 60 kDa, each containing in its active center a heme group and NADPH. Catalase has two enzymatic activities depending on the concentration of H2O2. If the concentration of H2O2 is high, catalase acts catalytically, i.e. removes H2O2 by forming H2O and O2 (catalatic reaction). However, at a low concentration of H2O2 and in the presence of a suitable hydrogen donor, e.g. ethanol, methanol, phenol, and others, catalase acts peroxidically, removing H2O2, but oxidizing its substrate (peroxidatic reaction). The review article presents current knowledge about the structure, properties, and functions of catalase in living organisms.

Glutathione and GSH-dependent enzymes in patients with liver cirrhosis and hepatocellular carcinoma.

We investigated glutathione level, activities of selenium independent GSH peroxidase, selenium dependent GSH peroxidase, GSH S-transferase, GSH reductase and the rate of lipid peroxidation expressed as the level of malondialdehyde in liver tissues obtained from patients diagnosed with cirrhosis or hepatocellular carcinoma. GSH level was found to be lower in malignant tissues compared to adjacent normal tissues and it was higher in cancer than in cirrhotic tissue. Non-Se-GSH-Px activity was lower in cancer tissue compared with adjacent normal liver or cirrhotic tissue, while Se-GSH-Px activity in cancer was found to be similar to its activity in cirrhotic tissue and lower compared to control tissue. An increase in GST activity was observed in cirrhotic tissue compared with cancer tissue, whereas the GST activity in cancer was lower than in adjacent normal tissue. The activity of GSH-R was similar in cirrhotic and cancer tissues, but higher in cancer tissue compared to control liver tissue. An increased level of MDA was found in cancer tissue in comparison with control tissue, besides its level was higher in cancer tissue than in cirrhotic tissue. Our results show that the antioxidant system of cirrhosis and hepatocellular carcinoma is severely impaired. This is associated with changes of glutathione level and activities of GSH-dependent enzymes in liver tissue. GSH and enzymes cooperating with it are important factors in the process of liver diseases development.

[Arginase activity in blood serum of patients with acute and chronic pancreatitis]. / Aktywnosc arginazy w surowicy chorych na ostre i przewlekle zapalenie trzustki.

UNLABELLED: Pancreatitis is the most common disease of the pancreas. Difficulties in early recognition of pancreatitic diseases, particularly chronic pancreatitis, are the reason of the search for new diagnostic methods. In our earlier studies we have shown that the determination of arginase activity in serum of patients with pancreatic cancer may be useful test in preoperative diagnosis of this cancer. The aim of this study was to asses the arginase activity in serum of patients with acute and chronic pancreatitis before and after medical treatment. MATERIAL AND METHODS: Arginase activity was studied in serum of 10 patients with acute and 10 patients with chronic pancreatitis obtained before, after and/or during the medical treatment. RESULTS: The increase of arginase activity was observed in both studied groups before the medical treatment, and a statistically significant decrease after the treatment (p < 0,05). There were not significant differences between arginase activity in acute and chronic pancreatitis. CONCLUSION: Arginase activity determination seems to be useful in monitoring the treatment of patients with acute and chronic pancreatitis.

[Activity of antioxidant enzymes in patients with liver cirrhosis]. / Aktywnosc enzymów antyoksydacyjnych u chorych z marskoscia watroby.

The aim of our studies was the estimation of activities of antioxidant enzymes in patients with liver cirrhosis. We investigated activities of superoxide dismutases (CuZnSOD, MnSOD), catalase (CAT), selenium dependent GSH peroxidase (Se-GSH-Px), selenium independent GSH peroxidase (non-Se-GSH-Px), GSH-S-transferase (GST), GSH reductase (GSHR) and the level ofreduced gutathione (GSH) in cirrhotic and healthy liver tissues. The activities of CuZnSOD, MnSOD, CAT and GSH-dependent enzymes (except GSHR) were found to be lower in cirrhotic tissue compared to healthy liver. Those changes were associated with decrease of GSH level in cirrhotic tissue compared with control liver tissue. Our results show that antioxidant barrier in liver cirrhosis is impaired. It is associated with decrease of glutathione level and changes of activities of antioxidant enzymes (SOD, CAT, GSHPx, GST, GSHR) in liver cirrhosis compared with healthy liver.

[Antioxidant barrier in patients with gastric cancer--preliminary study]. / Bariera antyoksydacyjna u chorych na raka zoladka--badania wstepne.

UNLABELLED: Gastric carcinoma is one of the most common malignancies of causes of cancer death world-wide, although its incidence and mortality and decreasing, particularly in developed countries. One of the many factors in its etiopathogenesis are free oxygen radicals and their derivatives, excess of which comes from disturbances of enzymatic and nonenzymatic mechanisms of antioxidant barrier. The aim of this study was the evaluation activities of antioxidant enzymes: superoxide dismutase (CuZnSOD, MnSOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione transferase (GST), glutathione reductase (GSH-R) as well as measurement of glutathione (GSH) and malondialdehyde (MDA) levels both in tissues (cancer and healthy) and in blood serum obtained from patients with gastric cancer. RESULTS: MnSOD and glutathione dependent enzymes (GSH-Px, GST, GSH-R) activities in gastric cancer were found to be higher than those in healthy stomach tissues. In pre- and postoperative blood serum from patients with gastric cancer was observed increase of CAT and GST as well as decrease of CuZnSOD and GSH-Px compared with the blood serum from healthy blood donors (control group). In preoperative blood serum from patients with gastric cancer GSH-R activity was lower than in control serum, whereas in postoperative serum it was higher compared with serum of the control group. Reduced GSH level was found to be lower in gastric cancer than this in healthy stomach tissue, adjacent to the cancer. Its level was also lower in pre- and postoperative blood serum of patients with gastric cancer compared with level in control serum. MDA concentration was found to be much higher in gastric cancer than this in healthy stomach tissue, whereas weren't significant differences between level of MDA in pre- and postoperative blood serum. CONCLUSION: Our results showed that functioning of antioxidant barrier of organism is severely impaired in patients with gastric cancer.

[Role of L-carnitine in metabolism, nutrition and therapy]. / Rola L-karnityny w przemianach, zywieniu i terapii.

The review article presents the biosynthesis, metabolism, sources, levels, and general functions of L-carnitine, a naturally occurring compound widely distributed in the body. It is synthesized in the liver, kidney, and brain and carriers long-chain fatty acids into the mitochondria for beta-oxidation and energy production. L-carnitine plays an important role in the translocation of acetyl moieties from the mitochondria to the cytoplasm for acetylcholine synthesis in neurones. Other roles--include removal of excess acyl groups, peroxisomal fatty-acid oxidation, and antioxidant activity.

[Arginine--metabolism and functions in the human organism]. / Arginina--metabolizm i funkcje w organizmie czlowieka.

L-arginine plays important roles in the metabolism of an organism. It is the precursor for the synthesis of proteins and other molecules of great biological importance, including nitric oxide, ornithine, polyamines, agmatine, proline, glutamate, creatine, dimethylarginine, and urea. For young organisms arginine is an essential amino acid for optimal growth and development, and must therefore be provided in the diet. For adults, arginine is a conditionally essential amino acid, especially in such conditions as trauma, burn injury, small-bowel resection, and renal failure. L-arginine administration improves cardiovascular, pulmonary, immune, and digestive functions and protect against the early stages of cancerogenesis.

[Usefulness of postoperative assay of arginase activity in blood serum of women after breast cancer resection]. / Przydatnosc pooperacyjnego oznaczania aktywnosci arginazy w surowicy kobiet po resekcji raka sutka.

The usefulness of arginase test was evaluated in follow-up of patients after breast cancer resection. The arginase activity was measured in blood serum of 970 patients from January 1996 to December 2000. The arginase activity above the normal value was detected in serum of 539 (55.6%) women. Only 197 (20%) patients demonstrated metastases and recurrence (true positive), 342 (35%) patients were disease free. The normal value of arginase activity was found in blood serum of 431 (44.4%) patients, 360 (36%) of them showed complete remission, whereas 71 (8%) demonstrated recurrence or metastases (false negative). Sensitivity of arginase test in post-surgery diagnostics of breast cancer was 73%. Measuring of arginase activity in blood serum of patients after breast cancer resection may be useful as an additional test confirming the disease dissemination.

Clinical significance of arginase after liver transplantation.

Liver graft function after transplantation is dependent on ischemia-reperfusion injury, toxicity of drugs (immunosuppression, antibiotics and other) and transplant rejection. Although routinely monitored with enzymatic tests (AST, ALT, GGT, ALP), bilirubin and coagulation parameters, differentiation between these pathologies is hardly possible without liver biopsy. Arginase (3.5.3.1) mostly exists in the liver and in trace amounts in extra-hepatic tissue. Thus, we hypothesized that activity of arginase could be a more specific test of liver function. Sera of 32 liver transplant recipients were tested for AST, ALT, ATIII, bilirubin and arginase. Samples were obtained daily in first 2 weeks after LTx and weekly afterwards. Correlation of arginase activity with other liver function markers was calculated. Serum arginase peaked at day 1 post LTx (mean 64,6+/-91 IU/L), and decreased more rapidly than other tests if good liver function was observed. The values showed strong and significant correlation with AST and ALT activities (Pearsons R 0,65 and 0,47 respectively). We conclude that activity of arginase in the serum is an exact test of liver function.

[Usefulness of preoperative assay of arginase in pancreatic cancer patients]. / Przydatnosc przedoperacyjnego oznaczania arginazy u chorych na raka trzuski.

The utility of new arginase test in detecting of pancreatic cancer was evaluated. The arginase level in blood serum of 72 patients were also compared with the concentration of Ca 19-9 and CEA antigens. Arginase activity was elevated in 60% patients, whereas the level of Ca 19-9 and CEA were increased in 64.5% and 45% patients, respectively. Sensitivity and specificity of arginase test and Ca 19-9 were similar, and were much higher then those of CEA antigen. However, antigen Ca 19-9 was more discriminating as compared to arginase test, and combined assessment did not improved the results of Ca 19-9. Arginase test needs further investigations, but it seems, that this cheap and very simple procedure can be useful as an additional tool for detection of pancreatic cancer.