ABSTRACT
The toxic naphthoquinone juglone (5-hydroxy-1,4-naphthoquinone) is efficiently degraded by the ligninolytic fungus Pleurotus sajor-caju, as demonstrated by the total bleaching within 9 d of a conventional liquid culture medium supplemented with 0.6 mM juglone. The oxidative degradation involves the production of hydrogen peroxide arising from both enzymic and non-enzymic oxidation reactions, promoted by the fungus. Juglone is not directly attacked by the oxidative enzymes of the ligninolytic machinery of P. sajor-caju, such as laccase, manganese peroxidase and arylalcohol oxidase. On the other hand, this naphthoquinone is a good substrate for a reductase, which triggers an auto-oxidative process producing reactive oxygen species and leading to juglone degradation. The degradation process continues to completion by means of a direct, presumably non-catalysed reaction with hydrogen peroxide.
Subject(s)
Naphthoquinones/metabolism , Pleurotus/metabolism , Alcohol Oxidoreductases/metabolism , Biodegradation, Environmental , Lignin/metabolism , Peroxidases/metabolism , Reactive Oxygen Species/metabolismABSTRACT
Epidemiologic evidence in humans suggests a role for selenium in reducing cancer incidence and mortality. The aim of the present study was that to assess the ability of selenium dioxide (SeO2) to enhance the lymphocyte progression through the cell cycle in patients with advanced (stage IV) cancer. Ten patients (mean age 51.9 years, range: 32-74; M/F ratio: 3/7) with tumors at different sites were included in the study. The addition into culture of SeO2 1.5 microM enhanced significantly the progression into S phase of PBMCs isolated from cancer patients, whilst no significant effect was observed on PBMCs isolated from controls. ROS levels were significantly higher, whereas GPx activity was significantly lower in cancer patients than controls. Serum levels of IL-6 and TNFalpha were significantly higher in cancer patients than controls. Our results show the ability of selenium to induce a progression of PBMCs from cancer patients into the cell cycle, which is an essential prerequisite for the physiological functioning of the immune system and thus positively influence the immune status of advanced cancer patients. The mechanism of action of selenium could be to downregulate the production and release of proinflammatory cytokines, which have a role in cancer progression and particularly in the onset of cachexia.
Subject(s)
Cell Cycle , Lymphocytes/metabolism , Neoplasms/metabolism , Selenium Compounds/pharmacology , Adult , Aged , Body Mass Index , Cachexia , Case-Control Studies , Disease Progression , Female , Glutathione Peroxidase , Humans , Interleukin-6/metabolism , Leukocytes, Mononuclear , Male , Middle Aged , Neoplasms/immunology , Neoplasms/pathology , Oxidative Stress , Reactive Oxygen Species/metabolism , Selenium Oxides , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In advanced cancer patients, the oxidative stress could take place either at the onset of disease or as a function of disease progression. To test this hypothesis, the following parameters were investigated: the erythrocyte activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), the serum activity of glutathione reductase (GR) and the serum total antioxidant status (TAS). The total antioxidant capacity of plasma LMWA was evaluated by the cyclic voltammetry methodology. We further determined the serum levels of proinflammatory cytokines (IL-6 and TNFalpha), IL-2, leptin and C-reactive protein (CRP). All of these parameters have been correlated with the most important clinical indices of patients such as Stage of disease, ECOG PS and clinical response. Eighty-two advanced stage cancer patients and 36 healthy individuals used as controls were included in the study. Our findings show that SOD activity was significantly higher in cancer patients than in controls and GPx activity was significantly lower in cancer patients than in controls. Serum values of IL-6, TNFalpha and CRP were significantly higher in patients than in controls. Serum leptin values of cancer patients were significantly lower than controls. SOD activity increased significantly from Stage II/ECOG 0-1 to Stage IV/ECOG 0-1, whereas it decreased significantly in Stage IV/ECOG 3. GPx activity decreased significantly in Stage IV/ECOG 2-3. An inverse correlation between ECOG PS and serum leptin levels was found. Serum levels of IL-2 decreased from Stage II/ECOG 0-1 to Stage IV/ECOG 2-3. A direct correlation between Stage/ECOG PS and serum levels of both IL-6 and CRP was observed. Cisplatin administration induced a significant increase of GPx after 24 hr. In conclusion, this is the first study that shows that several "biological" parameters of cancer patients such as antioxidant enzyme activity, cytokines, leptin and CRP strictly correlate with the most important clinical parameters of disease such as Stage and ECOG PS.
Subject(s)
Interleukin-6/blood , Leptin/blood , Neoplasms/metabolism , Oxidative Stress , Adult , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Cisplatin/pharmacology , Female , Glutathione Peroxidase/metabolism , Humans , Interleukin-2/blood , Male , Middle Aged , Neoplasm Staging , Neoplasms/blood , Neoplasms/pathology , Superoxide Dismutase/metabolismABSTRACT
The active site of tyrosinase is described with a view to depicting its interactions with substrates and inhibitors. Occurrence and mechanism(s) of tyrosinase-mediated browning of agrofood products are reviewed, with regard to both enzymic and chemical reactions, and their control, modulation, and inhibition. Technical and applicational implications are discussed.
