ABSTRACT
Metformin reduces blood glucose levels predominantly by inhibiting hepatic gluconeogenesis, although it also may enhance insulin receptor number or activity. The full effects of metformin are still poorly understood. In this study the effects of metformin on plasma xanthine oxidase (XO) activity, thiobarbituric acid-reactive substance (TBARS), lactate and fructosamine concentration as well as erythrocyte antioxidant enzyme activities were investigated in 46 patients with type 2 diabetes mellitus. All parameters were measured simultaneously just before metformin therapy (T0), 1 month (T1) and 2 months (T2) later. Results were compared with placebo and control group. We noted significant decrease in XO activity and in TBARS concentration (p<0.001) during monotherapy with metformin vs. placebo and T0 group. A significant correlation was observed between the activity of XO and the concentration of fructosamine (p<0.001). Erythrocyte glutathione peroxidase showed significantly lower activity in T2 group in comparison with T0 group (p<0.01). It is known that diabetic patients produce more TBARS as a result of enhanced free radical generation the source of which may also be the large amounts of XO produced following the conversion of xanthine dehydrogenase in hypoxic diabetic tissues. Thus, our results indirectly suggest that metformin can reduce toxic tissue damage through the inhibition on XO activity.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Hypoxia/drug therapy , Metformin/therapeutic use , Antioxidants/metabolism , Catalase/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Hypoxia/metabolism , Hypoxia/physiopathology , Male , Middle Aged , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Xanthine Oxidase/metabolismABSTRACT
Puromycin aminonucleoside (PAN) nephropathy in rats has been induced by the intraperitoneal injections of PAN. One group of animals which received PAN has been treated simultaneously with captopril (angiotensine converting enzyme-ACE-inhibitor) with the aim to test whether continuing treatment with captopril along with PAN injections would be able to modulate the toxic effects of PAN. The third group of rats was given only captopril. Morphological changes in the kidney were evaluated by scanning electron microscopy that showed the loss of podocyte foot processes in the kidney of PAN treated animals but also in the kidney of captopril treated ones as well as in the animals treated with both drugs simultaneously. Reduced glutathione content, catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase activities as well as lipid peroxides were investigated in rat blood and kidney. Captopril given alone produced a significant decrease of plasma lipid peroxides, but it did not show any significant effect on investigated antioxidative factor levels neither in blood nor in the kidney. PAN given alone produced a significant depletion of plasma lipid peroxides, kidney catalase and erythrocyte GSH-Px activity as well as a significant increase of plasma catalase and erythrocyte SOD activity. Treatment of animals with both drugs simultaneously resulted in a significant increase of erythrocyte SOD activity and a significant decrease of plasma lipid peroxides, erythrocyte GSH-Px and kidney SOD activities. Kidney xanthine oxidase activity showed a significant increase in both PAN and PAN plus captopril treated animals in comparison with the values of captopril treated rats. These data suggest that PAN changes the antioxidative factor pattern in rat blood and kidney. Contrary to our expectations that captopril may protect the toxic effects of PAN it only to a certain extent modifies these effects showing protective effect only on tissue catalase activity.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Anti-Bacterial Agents/adverse effects , Captopril/pharmacology , Oxidative Stress/drug effects , Puromycin/adverse effects , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Animals , Captopril/administration & dosage , Catalase/analysis , Glutathione/analysis , Glutathione Peroxidase/analysis , Kidney/drug effects , Kidney/ultrastructure , Male , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/analysis , Xanthine Oxidase/analysisABSTRACT
This study is aimed at examining whether essential arterial hypertension (HTN) or ACE inhibitors have any effect on erythrocyte selenium (Se)-dependent and Se-non-dependent glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity. Eleven patients with HTN (2 men and 9 women) and 9 healthy volunteers were included in this study after clinical examination and laboratory investigation. The activities of all three enzymes were determined and then the patients were assigned to receive ACE inhibitor therapy consisting of captopril, 25 to 50 mg daily, or enalapril, 10 to 40 mg daily. After 1 year, the determination of antioxidant enzymes was repeated. Our results showed that the initial values of Se-dependent GSH-Px in patients treated with ACE inhibitors were significantly lower (19.60 +/- 3.50 microM NADPH/min(-1)/mgHb(-1)) compared with the controls (28.64 +/- 4.93 microM NADPH/min(-1)/mgHb(-1); p < 0.001), whereas the activity of Se-non-dependent GSH-Px was significantly enhanced (13.55 +/- 1.46 microM NADPH/min(-1)/mgHb(-1); p < 0.001) compared with the control group (9.44 +/- 0.81 microM NADPH/min(-1)/mgHb(-1); p < 0.001). ACE inhibitors did not significantly change the activity of Se-dependent GSH-Px or Se-non-dependent GSH-Px. No significant alteration was observed in SOD activity.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Captopril/therapeutic use , Enalapril/therapeutic use , Erythrocytes/enzymology , Glutathione Peroxidase/blood , Hypertension/drug therapy , Hypertension/enzymology , Selenium/blood , Adult , Aged , Female , Humans , Hypertension/blood , Male , Middle Aged , Superoxide Dismutase/bloodABSTRACT
We studied the activity of erythrocyte selenium (Se)-dependent, Se-non-dependent glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in uremic patients (UP) in clinically healthy members from families affected with Balkan nephropathy (HMF/BEN) and in healthy volunteers from endemic settlements (control group). The SOD activity was not significantly different in the groups studied and the Se-non-dependent GSH-Px activity in HMF/BEN and UP was not different from the control group. However, the activity of Se-dependent GSH-Px in UP was lower compared with the control group, whereas the mean value of the Se-dependent GSH-Px activity in HMF/BEN was not significantly different when compared with the other two investigated groups.
Subject(s)
Balkan Nephropathy/enzymology , Glutathione Peroxidase/blood , Selenium/blood , Balkan Nephropathy/blood , Balkan Nephropathy/physiopathology , Creatinine/blood , Erythrocytes/enzymology , Humans , Kidney/physiopathology , Superoxide Dismutase/blood , Urea/bloodABSTRACT
Progression of some renal diseases is characterized by generation of reactive oxygen metabolites that are also involved in the pathophysiology of obstructive nephropathy. Catalase activity and lipid peroxidation were investigated in rats with unilaterally (UUL) and bilaterally ligated ureters (BUL). Forty-eight hours after ligation, the animals were sacrificed, and enzyme activity as well as the malondialdehyde (MDA) concentration were measured in the plasma, kidneys and livers. The activity of catalase was significantly reduced in the plasma of the BUL rats and in the kidneys of both investigated groups. In the liver, catalase activity was decreased only in the BUL group. The MDA concentration in the plasma and kidneys of the BUL rats was significantly increased while in the liver it remained unchanged. These results suggest that lipid peroxidation in the induced uremic state could be responsible for catalase inactivation.
Subject(s)
Catalase/metabolism , Lipid Peroxidation , Ureter/physiology , Animals , Catalase/blood , Kidney/metabolism , Ligation , Liver/metabolism , Male , Malondialdehyde/blood , Malondialdehyde/metabolism , Rats , Rats, Wistar , Urea/blood , Ureter/surgeryABSTRACT
In 14 patients (4 males and 10 females) with systemic hypertension plasma and erythrocyte lipid peroxides, plasma and erythrocyte catalase activity, plasma glutathione S-transferase (GST) activity, blood reduced glutathione (GSH) content and erythrocyte oxidant stress were investigated. All parameters were performed after clinical examination and then the patients were assigned to receive ACE inhibitor therapy, captopril (25-50 mg given twice per day) or enalapril (10-40 mg given twice per day). After six months the determination of lipid peroxides and antioxidative factors was repeated. At the beginning of the study both treated groups showed significantly higher plasma lipid peroxides compared to the control group. Both used ACE inhibitors produced significant decrease of plasma lipid peroxides after six months. Blood GSH content was also significantly higher in both patient groups before the treatment compared to the controls. Neither captopril nor enalapril produced any significant effect on GSH. Initial values of plasma GST activity in the patients were similar to the control group and did not significantly change after six month treatment. The patients assigned to receive enalapril showed significantly enhanced initial plasma catalase activity according to the controls. After six months treatment both ACE inhibitors significantly decreased plasma catalase activity. Erythrocyte lipid peroxides, erythrocyte catalase activity and oxidant stress of erythrocytes in both groups studied neither differ significantly at initial time of investigation according to the control group nor during or after six month treatment.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Catalase/blood , Glutathione Transferase/blood , Glutathione/blood , Hypertension/blood , Lipid Peroxides/blood , Adult , Aged , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Captopril/therapeutic use , Enalapril/therapeutic use , Erythrocytes/drug effects , Erythrocytes/metabolism , Female , Humans , Hypertension/drug therapy , Male , Middle AgedABSTRACT
Etiology and pathogenesis of endemic nephropathy (EN) are unknown and in this work the possible pathogenetic role of disturbed antioxidant protection, estimated by the activity of erythrocyte catalase, was evaluated. In patients with EN as well as in clinically healthy members of their families a statistically significant increase in catalase activity (16.7 +/- 0.63 x 10(4) U/g Hb) compared to the control group of the blood bank donors from the city of Nish (11.7 +/- 0.69 x 10 U/g Hb) was found. Increased catalase activity, at the level of significance, was also found in clinically healthy members of EN patients families. The increase of catalase activity was considered compensatory to the increased oxydative capacity.
Subject(s)
Balkan Nephropathy/blood , Catalase/blood , Erythrocytes/enzymology , Family Health , HumansABSTRACT
Balkan endemic nephropathy (BEN) is a chronic progressive kidney disease leading to renal insufficiency. The possible etiological role of some toxic factors was considered in this study by investigating the activity of erythrocyte delta-aminolevulinate dehydratase (ALA-D), an enzyme influenced by various environmental factors. We observed that ALA-D activity was markedly decreased in patients with BEN and in 32% of their healthy family members. Glutathione concentration was found normal in all the groups studied, however, it was possible to reactivate the enzyme in vitro by addition of exogenous glutathione. Percent activation was significantly higher in the groups with decreased ALA-D activity. Blood lead levels were within normal range. The results suggest a normal synthesis of ALA-D apoenzyme, and also the presence of some factors, environmental, metabolic, or genetic, which may affect the enzyme activity through binding to the reactive groups in the active center of this enzyme or by oxidation of the reactive groups. Additional studies are necessary to further elucidate the significance of decreased ALA-D activity in BEN and their healthy relatives.