The principal metabolic effect of metformin-an oral antihyperglycaemic agent-is the improvement in the sensitivity of peripheral tissues and liver to insulin. This study examined the effect of metformin monotherapy on antioxidative defence system activity in erythrocytes and plasma in diabetic patients. We studied the effect of metformin treatment on the activities of Cu, Zn-superoxide dismutase (EC 1. 15. 1. 1.), catalase (EC 1. 11. 1. 6.) and glutathione peroxidase (EC 1. 11. 1. 9.) in relation to lipid peroxidation products and reduced glutathione level in plasma and erythrocytes. In this study we also examined erythrocytes' susceptibility to H2O2-induced oxidative stress during metformin therapy. Although metformin monotherapy ameliorated the imbalance between free radical-induced increase in lipid peroxidation (by reducing the MDA level in both erythrocytes and plasma) and decreased plasma and cellular antioxidant defences (by increasing the erythrocyte activities of Cu, Zn, SOD, catalase and GSH level) and decreased erythrocyte susceptibility to oxidative stress, it had negligible effect to scavenge Fe ion-induced free radical generation in a phospholipid-liposome system.

Glucocorticoids (GC) are used widely for the treatment of patients with various disorders, including autoimmune diseases, allergies, and lymphoproliferative disorders. Glucocorticoid therapy is often limited by several adverse reactions associated with GC excess. Excess GC can elicit a variety of symptoms and signs, including growth retardation in children; immunosuppression; cardiovascular disorders like hypertension and atherosclerosis; osteoporosis; myopathy; and diabetes mellitus. Currently, attention is focused on oxidative stress as one of the major determinants of endothelial dysfunction and cardiovascular senescence. The main reason for all unwanted effects of GC is that dexamethasone induces the overproduction of reactive oxygen species, causing dysregulation of physiological processes. Humans and animals with GC-induced hypertension exhibit reduced nitric oxide levels; patients with excess GC levels also suffer from depression as a consequence of low levels of serotonin and melatonin. The common cofactor for the production of these vasoactive molecules is tetrahydrobiopterin (BH4), which is required for nitric oxide synthesis.

Under physiological conditions insulin controls the metabolism of carbohydrates, lipids and proteins. Diabetes mellitus is a metabolic disease characterized by a disturbance in the intermediary metabolism of glucose and glucose-induced insulin release. Arginase (L-arginine amidinohydrolase, EC 3.5.3.1) modulates nitric oxide synthase activity by regulating intracellular L-arginine availability. In diabetes mellitus, a decrease in nitric oxide bioavailability is a central mechanism for endothelial dysfunction. The aim of our study was to assess arginase activity in the blood of children with diabetes mellitus. Blood arginase activity, serum glucose (14.155 +/- 4.197 mmol/L; p < .001) and blood HbA1c (11.222 +/- 3.186 %; p < .001), were significantly higher in diabetic children than in healthy controls, whereas the magnesium (Mg2+) level, a cofactor of many enzymes, was significantly lower (0.681 +/- 0.104 micromol; p < .001). In diabetic children, arginase activity, hyperglycemia (r = 0.143), and the HbA1, level (r = 0.381) showed a positive correlation between but a negative correlation between Mg2+ and arginase activity (r= -0.206). The higher arginase activity and the lower Mg2+' levels in diabetic children could be a consequence of reduced insulin action and increased protein catabolic processes in these pathophysiological conditions. The inverse directions of arginase activity and serum Mg2+ levels are in agreement with this concept.

The results demonstrate that the RNA-degrading pathway in Fas-induced apoptosis can accelerate the liberation of the latent enzyme from the inhibitor complex. IFN-alpha prevented enormous, Fas-ligand induced degradation of all the substrates used in this experimental study, most probably due to similarities in the signal transduction pathways. Investigations of death receptor-induced apoptosis may lead to novel treatment combinations for patients with acute or chronic liver diseases.

Cadmium is a widespread, toxic industrial pollutant. The proximal tubule of the mammalian kidney is a major target of Cd-induced toxicity. We analyzed the effects of cadmium exposure on the model system of experimental animals, the thiobarbituric acid (TBA)-reactive substance (TBARS) level, and the activity of xanthine oxidase (XO) and catalase in kidney of rats, with and without glutathione and lipoic acid (LA). The experimental animals were classified into six groups, regarding cadmium, glutathione, and LA intake. The concentration of TBARSs in the homogenate was determined by spectrophotometric method according to Nabavi et al. The specific activity of XO was determined spectrophotometrically by the method of Aygul et al. Catalase activity in tissues was determined by spectrophotometric method according to Nabavi et al. The increased level of TBARS and the increased activity of XO in kidney tissue in cadmium poisoning are statistically significant compared to control (p < 0.001). Glutathione and LA applied along with cadmium lowered TBARS concentration and reduced XO activity (p < 0.001). Catalase activity in the kidney tissue was increased in the group, which was administered cadmium (p < 0.001). In conclusion, glutathione and LA, as physiological antioxidants applied with cadmium, have reduced the level of lipid peroxide and the activity of XO, and can be used as protectors in conditions of cadmium poisoning.