ABSTRACT
Toxic effects of ethylene glycol (EG) and its metabolites are mainly related to metabolic acidosis and kidney damage. EG biotransformation involving CYP2E1 affects the oxidant-antioxidant balance. The study assessed the effect of repeated administration of 4-methylpyrazole (4MP, 15mg/kg b.w. after 2h, followed by 10mg/kg b.w. every 12h) on renal function (creatinine, urea and urinary protein levels) as well as products of kidney's lipid peroxidation (MDA and TBARS levels) in rats poisoned with EG (5745mg/kg b.w.). Serum EG and glycolic acid (GA) concentrations were measured throughout the experiment. Repeated administration of 4MP reduced the rate of EG elimination, extended the period of EG persistence in serum and significantly limited formation of GA. The study showed the temporary intensification of kidney oxidative processes that correlated with changes in kidney function. It was found that the use of 4MP in EG poisoning inhibited its biotransformation to toxic metabolites, but simultaneously intensified oxidative damages in kidneys.
Subject(s)
Antidotes/administration & dosage , Ethylene Glycol/poisoning , Kidney Diseases/metabolism , Kidney/drug effects , Lipid Peroxidation/drug effects , Pyrazoles/administration & dosage , Animals , Antidotes/adverse effects , Biotransformation , Cytochrome P-450 CYP2E1/metabolism , Dose-Response Relationship, Drug , Drug Administration Schedule , Fomepizole , Kidney/metabolism , Kidney/physiopathology , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , Kidney Function Tests , Male , Pyrazoles/adverse effects , Rats , Rats, WistarABSTRACT
OBJECTIVES: The aim of the study was to evaluate the influence of acetylsalicylic acid (ASA) on benzene hematotoxicity in rats. MATERIALS AND METHODS: The study was carried out on rats exposed for 2, 4 and 8 weeks to benzene vapour at a concentration of 1.5 or 4.5 mmol/m(3) of air (5 days per week, 6 hours per day) alone or together with ASA at the doses of 5, 150 or 300 mg/kg body weight (per os). RESULTS: Benzene at a concentration of 4.5 mmol/m(3) caused a slight lymphopenia, granulocytosis and reticulocytosis in blood. In bone marrow traits of megaloblastic renewal, presence of undifferentiated cells and giant forms of granulocytes as well as an increase in myeloperoxidase and decrease in chloroacetate esterase activity and lipids content were noted. ASA (150 and 300 mg/kg b.w.) influenced some of hematological parameters, altered by benzene intoxication. ASA limited the solvent-induced alteration in blood reticulocyte count and in the case of bone marrow in the erythroblasts count. Traits of megaloblastic renewal in bone marrow were less pronounced. Besides, higher activity of myeloperoxidase and the decrease in the level of lipids in granulocytes were noted. CONCLUSION: Our results suggest that ASA limited the benzene-induced hematotoxicity.
Subject(s)
Aspirin/pharmacology , Benzene/toxicity , Bone Marrow Cells/drug effects , Cyclooxygenase Inhibitors/pharmacology , Hematologic Diseases/blood , Hematologic Diseases/chemically induced , Inhalation Exposure/adverse effects , Animals , Carboxylic Ester Hydrolases/metabolism , Hematologic Diseases/enzymology , Male , Peroxidase/metabolism , Rats , Rats, Wistar , Reticulocyte CountABSTRACT
BACKGROUND: The aim of the conducted studies was to evaluate the effect of 4-methylpyrazole, increasingly used in detoxifying treatments after ethylene glycol poisoning, on the activity of some antioxidant enzymes and lipid peroxidation formation in the liver of rats after experimental co-exposure to ethylene glycol and ethyl alcohol. METHODS: The trials were conducted on adult male Wistar rats. Ethylene glycol (EG) at the dose of 3.83 g/kg bw and ethyl alcohol (EA) at the dose of 1 g/kg bw were administered po, and 4-methylpyrazole (4-MP) at the dose of 0.01 g/kg bw was administered ip. Parameters of antioxidant balance were evaluated in hepatic cytosol, including the activity of the following enzymes: glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and lipid peroxidation level (TBARS). RESULTS: The results suggest that evaluation of the effects of administrated 4-MP after co-exposure to EG and EA in the liver revealed statistically significant changes on antioxidant enzyme system and malondialdehyde formation. CONCLUSION: The changes in biomarkers activity indicate a greater production of free radicals which exceeds the capability of antioxidant system, appearing with oxidative stress in the group of animals treated by 4-MP combined with EG and EA.
