Joanna Kowalówka-Zawieja

Effect of 4-methylpyrazole on antioxidant enzyme status and lipid peroxidation in the liver of rats after exposure to ethylene glycol and ethyl alcohol

BACKGROUNDnThe 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.nnnMETHODSnThe 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).nnnRESULTSnThe 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.nnnCONCLUSIONnThe 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.

Effect of repeated administration of 4-methylpyrazole on renal function and lipid peroxidation products in rat kidney after ethylene glycol poisoning

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 kidneys 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.

Influence of acetylsalicylic acid on hematotoxicity of benzene

ObjectivesThe aim of the study was to evaluate the influence of acetylsalicylic acid (ASA) on benzene hematotoxicity in rats.Materials and MethodsThe 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/m3 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).ResultsBenzene at a concentration of 4.5 mmol/m3 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.ConclusionOur results suggest that ASA limited the benzene-induced hematotoxicity.

Metabolic interactions between acetylsalicylic acid and benzene

The aim of the study was to evaluate cytochrome P-450 dependent hepatic monooxygenases system and urinary excretions of phenol and muconic acid in animals subjected to acetylsalicylic acid (ASA) orally and benzene by inhalations. ASA increased urinary excretion of muconic acid although it did not affect the urinary level of phenol. Benzene decreased concentrations of P-450 and b(5) cytochromes and the activities of NADPH-cytochrome P-450 and NADH-cytochrome b(5) reductases. In rats exposed to ASA and benzene simultaneously the concentration of both cytochromes and the activity of the cytochrome dependent reductases was higher than in the rats exposed only to benzene and sometimes exceeded the control group values.