ABSTRACT
The study was undertaken to investigate the influence of specific inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1), in particular nicotinamide and 1,5-isoqinolinediol on white blood cells of rats with diabetes. Using the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate ROS production in leukocytes was asseced. It was found that the development of streptozotocin-induced diabetes was accompanied by an intensification of oxidative stress and a significant decrease in viability of blood leukocytes as compared to control animals. Administration of PARP-1 inhibitors prevented the development of oxidative stress in leukocytes and increased their viability. It was shown a reduction of superoxide dismutase activity in serum in diabetes. Investigated PARP-1 inhibitors had no effect on the activity of superoxide dismutase and glucose levels in the blood. The findings suggest the intensification of oxidative stress in leukocytes of diabetic animals and the ability of nicotinamide and 1,5-isoqinolinediol to prevent its development depending on the features of their structure.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Enzyme Inhibitors/pharmacology , Leukocytes/drug effects , Niacinamide/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors , Animals , Blood Glucose/analysis , Cell Survival/drug effects , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/pathology , Fluoresceins , Fluorescent Dyes , Isoquinolines , Leukocytes/enzymology , Leukocytes/pathology , Male , Oxidation-Reduction , Oxidative Stress , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerases/metabolism , Quinolines/pharmacology , Rats , Rats, Wistar , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Streptozocin , Superoxide Dismutase/metabolismABSTRACT
The study was undertaken to investigate the modulating effect of nicotinamide (NAm) in different concentrations and under different glucose concentrations on the viability and oxidative stress induced by streptozotocin (STZ, 5 mmol/l) and hydrogen peroxide (H2O2, 100 micromol/l) on isolated rat pancreatic cells of the Langerhans islets in vitro. Cell viability did not depend on the concentration of glucose in the range of 5-20 mmol/l, and in subsequent studies we used glucose in concentration of 10 mmol/l to protect cells against its hypo- and hyperglycemic action. Cytoprotective effect of NAm in concentrations from 5 to 20 mmol/l on cells survival was the same. It was found that the destructive action of STZ and H2O2 during 24 hours on isolated cells of the pancreas resulted in the significant cell death. It was revealed that NAm in concentration of 5 mmol/l not only had cytoprotective effects against STZ and H2O2 but also partially reduced the level of oxidative stress in the investigated cells induced by these compounds. High concentration of NAm, 35 mmol/l, causes cytotoxic effect on the viability of pancreatic islet cells and increase of oxidative stress induced by STZ and H2O2. Most likely these effects could be associated with direct modulatory action of NAm on important effector mechanisms involved in cell death, including PARP-dependent processes, or/and indirectly, through metabolic and antioxidant effects of the compound.
Subject(s)
Antioxidants/pharmacology , Islets of Langerhans/drug effects , Niacinamide/pharmacology , Reactive Oxygen Species/antagonists & inhibitors , Animals , Antioxidants/metabolism , Cell Survival/drug effects , Cells, Cultured , Cytoprotection , Dose-Response Relationship, Drug , Glucose/metabolism , Glucose/pharmacology , Hydrogen Peroxide/toxicity , Islets of Langerhans/cytology , Islets of Langerhans/metabolism , Male , Niacinamide/metabolism , Oxidative Stress/drug effects , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Streptozocin/toxicityABSTRACT
It was established that acute poisoning of rats by 1,2-dichloroethane induced considerable changes in lipid peroxidation indices, glutathione content and activity of antioxidant enzymes--superoxidase, catalase, glutathione peroxidase in the brain tissue, erythrocytes and blood plasma. It was shown that nicotinamide in the dose of 200 mg/kg prevented considerable degree of the intoxication caused by 1,2-dichloroethane as well as activation of lipid peroxidation and inhibition of antioxidant defens enzyme activities in tissue of experimental animals.
Subject(s)
Brain/drug effects , Erythrocytes/drug effects , Ethylene Dichlorides/poisoning , Niacinamide/therapeutic use , Oxidative Stress/drug effects , Vitamin B Complex/therapeutic use , Animals , Blood Proteins/metabolism , Brain/metabolism , Erythrocytes/metabolism , Lipid Peroxidation/drug effects , Male , Niacinamide/pharmacology , Poisoning/blood , Poisoning/metabolism , Poisoning/prevention & control , Rats , Rats, Wistar , Vitamin B Complex/pharmacologyABSTRACT
Alterations of Na+,K+-ATPase activity and serotoninergic system functioning were investigated in brain synaptosomes fractions of rats under experimental acute 1,2-dichloroethane (DChE) intoxication. It was shown that Na+,K+-ATPase activity was markedly increased (by 41,8%) in a period of 24 h after DChE intoxication and decreased (by 27%) after 48 h intoxication. The level of [2-14C]-serotonin uptake by synaptosomes was progressively diminished after 24 and 48 h after DChE injection whereas the activity of monoamine uptake proved to be unchanged. Nicotinamide (200 mg/kg of body weight) was administered to rats subjected to DChE 1, 24 and 36 h after poisoning. The treatment of rats with nicotinamide resulted in some normalization of brain synaptosomal Na+, K+-ATPase activity and serotonin uptake controlled at 48 h after DChE intoxication.
