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1

Wplyw niektorych inhibitorow ADH na aktywnosc mikrosomalnego systemu utleniania alkoholi in vitro

100%

Dawidek-Pietryka K. , Dudka J.

Roczniki Państwowego Zakładu Higieny

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2001

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tom 52

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nr 4

337-345

PL

W pracy oceniano wpływ amidu kwasu izowalerianowego, acetylo-L-karnityny, błękitu metylenowego, cymetydyny, DMSO, EDTA, o-fenantroliny, pirazolu, penicylaminy i teofiliny na aktywność mikrosomalnego systemu utleniania alkoholi. Badania przeprowadzono in vitro z enzymem pochodzącym z wątroby ludzkiej katalizującym reakcję utleniania metanolu.

EN

The treatment of methanol intoxication usually focuses on prevention of methanol conversion to its toxic metabolites due to administration of ethanol or 4-methylpyrasole (4-MP). Nevertheless there is a need for new measures treatment of methanol intoxication. For this reason the influence of some alcohol dehydrogenase inhibitors on the activity of microsomal alcohol oxidising system (MAOS) with methanol as a substrate was assayed. In the present study MAOS activity was measured spectrophotometrically in vitro at physiological pH 7.4 and 37°C, assaying the degree of methanol oxidation. The quantity of arising formaldehyde was measured according with the method of Nash. The source of enzyme was hepatic slices.

2

Methemoglobinemia oraz wybrane wskazniki biochemiczne funkcji watroby i nerek w subchronicznym narazeniu szczurow na rtec i azotyny

80%

Dudka J. , Dawidek-Pietryka K. , Szczepaniak S. , Leczynska D.

Bromatologia i Chemia Toksykologiczna

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2000

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tom 33

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nr 2

151-154

PL

Po 90-dniowym narażeniu szczurów per os w odstępach dobowych, na pojedyncze i łączne działanie HgCl2 (1,4 mg/kg m.c.) i NaNO2 (30 mg/kg m.c.) określono w pełnej krwi poziom methemoglobiny, a w osoczu aktywność aminotransferazy asparaginianowej (AspAT); [E.C.2.6.1.1.], aminotransferazy alaninowej (AlAT); [E.C.2.6.1.2 ], gammaglutamylotransferazy (GGTP-azy); [E.C.2.3.2.1.] oraz stężenie kreatyniny i mocznika.

EN

The aim of this work was to check whether mercury and nitrites given to rats at doses causing methaemoglobinaemia disturb the normal function of liver and kidneys. Four groups of male Wistar rats received for 3 months: 1) distilled water (control), 2) sodium nitrite at 30 mg/kg b.w./day, 3) mercuric (II) chloride at 1.4 mg/kg b.w./day, 4) mercuric chloride and sodium nitrite in amounts as above. Methaemoglobin level was determined in the whole blood, while AspAT, AlAT and GGTP activities and creatinine and urea levels were determined in blood plasma. Our results indicate that both mercury and nitrite increase methaemoglobin level in the blood. With combined exposure to mercury and nitrite, the increase was less evident. Increased AspAT and AlAT activities were observed in the rats receiving mercury, suggesting a toxic effect on hepatocyte membranes. A similar effect was observed in the rats receiving, in combination, mercury and nitrite. Mercury increases serum urea level, indicating a toxic effect of mercury on the kidneys under conditions of subchronic exposure.

3

Methemoglobinemia oraz wybrane parametry biochemiczne zwiazane ze stanem redox erytrocytu w subchronicznym narazeniu na rtec i azotyny

80%

Dudka J. , Dawidek-Pietryka K. , Szczepaniak S.

Bromatologia i Chemia Toksykologiczna

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1999

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tom 32

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nr 3

259-263

PL

Po З0, 60 і 90 dniach narażenia szczurów na pojedyncze i łączne działanie chlorku rtęci (II) - 1,4 mg/kg m c. x dzień i azotynów - 30 mg/kg m.c. x dzień, określono poziom methemoglobiny (Met-Hb). Po 90 dniach - w erytrocytach oznaczono poziom pozabiałkowych grup sulfliydrylowych (SH) oraz aktywność dehydrogenazy glukozo-6-fosforano- wej (G-6-PDH; E.C.l. 1.1.49.), peroksydazy glutationowej (GSH-Px; E.C. 1.11.1.9.) i dehydrogenazy mleczanowej (LDH; E.C. 1.1.1.27.). Wykazano, że rtęć, mimo własnego nieznacznego działania methemoglobinotwórczego, obniża methemoglobinotwórcze działanie azotynów. Zarówno rtęć, jak i azotyny obniżają poziom wolnych grup -SH. Stwierdzono istotne zmiany GSH-Px we wszystkich przebadanych grupach. Zaobserwowano podwyższoną aktywność LDH u szczurów otrzymujących azotyn i G-6-PDH w grupie narażonej na łączne działanie rtęci i azotynów.

EN

Four groups of male Wistar rats receiving per os daily doses of: 1) distilled water (control); 2) sodium nitrite (30 mg/kg b.w.); 3) mercuric chloride (1.4 mg/kg b.w.); 4) mercuric chloride and sodium nitrite in amounts as above. Blood methaemoglobin concentration was determined after 30, 60 and 90 days of the exposure. The level of free sulfhydryl groups and the activities of glucose-6-phosphatase dehydrogenase (G-6-PDH; E.C. 1.1.1.49), glutathione peroxidase (GSH-Px, E.C. 1.11.1.9), lactate dehydrogenase (LDH; E.C. 1.1.1.27) in erythrocytes were determined after 90 days. Methaemoglobincreative effect of nitrites after 30, 60 and 90 days of the exposure was observed. Mercury, despite its own methaemoglobincreative effect, reduced the methaemoglobincreative effect of nitrites. Both the nitrite and mercury decreased free sulfhydryl groups in erythrocytes. Reduced GSH-Px activity in the Hg and NaNO2 groups was observed. The rats receiving both mercury and nitrite were found to be characterised by increased GSH-Px activity. Also, higher LDH activity was observed in the nitrite-treated rats, while higher G-6-PDH activity was noted in the rats receiving mercury alone or mercury and nitrite.

4

Gazowo-chromatograficzna analiza metanolu w pelnej krwi na kolumnie z polimerem Poropak Q

80%

Szczepaniak S. , Dawidek-Pietryka K. , Dudka J.

Bromatologia i Chemia Toksykologiczna

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1997

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tom 30

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nr 4

337-341

PL

Wykazano przydatność chromatografu gazowego Varian Aerogra/2860 do oznaczania metanolu w pełnej krwi. Stwierdzono, że stosując odpowiednie parametry pracy można oznaczać metanol we krwi z dobrą precyzją (V = 6,6%) i dobrą dokładnością (odzysk = 98,3%) na kolumnie z Porapakiem Q, jako fazą stacjonarną.

EN

Methanol content of whole blood was analysed by gas chromatography on a Varian 2860 apparatus using Porapak Q column packing. A linear relationship was shown to exist between detector response and methanol concentrations within the range 0.2 to 2.0 mg/ml. Sample supernatants from precipitated blood containing acetonitrile as the internal standard were injected directly on column with Porapak Q. Under optimal conditions of the procedure (temperatures: 150°C injection port, 115°C column, 160°C detector; flow rates: 48 cm3/min. N2, 40 cm3/min H2, 240 cm3/min air) the precision of the method in terms of day-today coefficient of variation was 6.6%, with methanol recovery as high as 98.3%. The utility of the method was confirmed by determining, at different times since the exposure, levels of methanol in the blood of rats exposed to a dose of 2.8 g/kg.

5

Methemoglobinemia oraz niektore parametry biochemiczne zwiazane z funkcja watroby i nerek u szczurow podczas lacznego subchronicznego narazenia na olow i azotyny

80%

Dudka J. , Dawidek-Pietryka K. , Szczepaniak S. , Dudka K.

Bromatologia i Chemia Toksykologiczna

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1999

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tom 32

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nr 3

253-257

PL

Po 90-dniowym narażeniu szczurów, w odstępach dobowych, na pojedyncze i łączne działanie Pb(CH3COO)2 (10 mg/kg m.c.) i NaNO2 (30 mg/kg m.c.) oznaczono w pełnej krwi poziom methemoglobiny, a w osoczu aktywność aminotransferazy asparaginianowej (AspAT [EC.2.6.1.1]), aminotransferazy alaninowej (AlAT [EC.2.6.1.2]), gamma-glutamylotransferazy (GGTP-azy [EC. 2.3.2.1]) oraz stężenie kreatyniny i mocznika.

EN

The aim of this work was to verify the hypothesis that lead and nitrites given to rats at doses causing methaemoglobinaemia adversely affected the hepatic and renal functions. Male Wistar rats were used. They were divided into 4 groups which received for 3 months per os daily doses of: 1) distilled water (control); 2) sodium nitrite (30 mg/kg b.w.); 3) lead (II) acetate (10 mg/kg b.w.); 4) lead (II) acetate and sodium nitrite at doses as above. The level of methaemoglobin was determined in the whole blood. The activities of alanine aminotransferase (AlAT), aspartate aminotransferase (AspAT), gamma-glutamyltransferase (GGTP) and the levels of creatinine and urea were determined in the blood plasma. Our results show that not only the nitrite but also lead alone increased blood methaemoglobin level. The combined exposure to both xenobiotics revealed their antagonistic action on blood methaemoglobin level. There was an increase of blood serum A1AT and AspAT activities in the rats receiving lead, suggesting toxic action of lead on hepatocyte membranes. A comparable but stronger effect was observed in the rats receiving combined doses of lead and nitrite. Nephrotoxic effects were not observer either in the rats receiving lead alone or in combination with the nitrite.

6

Wplyw olowiu i azotynow na aktywnosc niektorych enzymow uczestniczacych posrednio w redukcji methemoglobiny u szczurow

80%

Dudka J. , Szczepaniak S. , Dawidek-Pietryka K. , Kusmierzak E.

Bromatologia i Chemia Toksykologiczna

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1998

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tom 31

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nr 3

233-237

PL

Po 90-dniowym narażeniu szczurów, w odstępach dobowych, na pojedyncze i łączne działanie Pb(CH3COO)2 i NaNO2 oznaczono aktywność peroksydazy glutationowej (GSH-Px; E.C.1.11.1.9.), dehydrogenazy mleczanowej (LDH; E.C.1. 1.1.27.) oraz dysmutazy ponadtlenkowej (SOD; E.C.1.15.1.1.). Stwierdzono istotne zmiany aktywności GSH-Px we wszystkich badanych grupach. Wzrost aktywności LDH zaobserwowano jedynie w grupie otrzymującej azotyn sodu.

EN

Mille Wistar rats for 3 months received per os: 1) distilled water (control); 2) 30 mg/kg b.w. per diem sodium nitrite (20% LD50); 3) 10 mg/kg b.w. per diem lead (II) acetate (6,7% LD50); 4) lead (II) acetate and sodium nitrite in amounts per diem as above. Activities of glutathione peroxidase (E.C. 1.11.1.9), lactate dehydrogenase (E.C.1. 1.1.27) and superoxide dismutase (E.C. 1.15.1.1.) in erythrocytes of all test animals were determined. Significant changes of glutathione peroxidase activity were shown to occur in all treated groups. Increased lactate dehydrogenase activity was observed only in the group receiving sodium nitrite. Changes in the activity of superoxide dismutase were not significant in any of the examined groups. It is quite likely that, at low methaemoglobin concentrations (in lead-poisoned rats), the main mechanism of methaemoglobin reduction is associated with glutathione peroxidase activation, while at higher methaemoglobin concentrations (in sodium nitrite poisoning), enzyme systems using reduced adenine dinucleotides are essential for methaemoglobin reduction.

7

Inhibicja dehydrogenazy alkoholowej przez wybrane zwiazki w reakcji z metanolem i glikolem etylenowym

80%

Dawidek-Pietryka K. , Dudka J. , Szczepaniak S.

Bromatologia i Chemia Toksykologiczna

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2000

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tom 33

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nr 2

155-160

PL

W pracy przedstawiono wyniki badań dotyczących hamowania dehydrogenazy alkoholowej jako enzymu pierwszego etapu biotransformacji alkoholi. Sprawdzono skuteczność następujących związków: fenylohydrazyny, acetylo-L-karnityny, 1,10-fenantroliny, amidu kwasu izowalerianowego, EDTA, dimetylosulfotlenku i penicylaminy w stężeniach 1,0; 0,10; 0,01 mol/dm3. Substratami enzymu był metanol w stężeniach 0,10 i 0,05 mol/dm3 oraz glikol etylenowy w stężeniu 0,10 mol/dm3.

EN

A rational management of alcohol intoxication could be based on the inhibition of alcohol hydrogenase (ADH), the first enzyme involved in the biotransformation of alcohols. Standard therapy for methanol and ethylene glycol intoxication comprises administration of ethanol to inhibit their oxidation by ADH to more toxic metabolites. The aim of this work was to find some human liver ADH inhibitors, other than ethanol. In the present study, ADH activity was estimated by spectrophotometry by assessing NADH absorbance in vitro at pH 7.4 and 37°C using human enzyme hepatic fraction. The inhibiting effect of six selected chemical compounds on ADH was tested and the residual activity of the enzyme inhibited by the selected chemicals in the reaction with 0.05 mol/dm3 and 0.10 mol/dm3 methanol and 0.10 mol/dm3 ethylene glycol as substrates was determined. The ADH activity was, to a varying extent, inhibited by all examined chemicals: acetyl-L carnitine, o-phenantroline, isovaleric acid amide, DMSO, EDTA, phenylohydrazine and penicillamine at 1.0; 0.10; 0.01 mmol/dm3. O-phenantroline proved to be the best inhibitor, both in the reaction with methanol and ethylene glycol.

8

Aktywnosc katalazy po zastosowaniu wybranych inhibitorow ADH i MEOS, badania in vitro w homogenatach watroby szczurow

80%

Dawidek-Pietryka K. , Dudka J. , Jagiello-Wojtowicz E.

Roczniki Państwowego Zakładu Higieny

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2003

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tom 54

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nr 4

373-381

PL

Prezentowana praca jest kontynuacją badań nad wpływem wybranych inhibitorów ADH i MEOS na pierwszy etap biotransformacji metanolu. Stosowano: 3-amino-1,2,4-triazol, cymetydynę, EDTA, 1,10-fenantrolinę i 4-metylopirazol w reakcji utleniania metanolu w stężeniach 0,05 i O, 10 mol/L Oceniano ich wpływ na aktywność katalazy w homogenatach wątroby szczurów.

EN

In the first pass methanol biotransformation three enzymatic systems: alcohol dehydrogenase (ADH), microsomal alcohol oxidising system (MEOS) linked with cytochrome P-450 and catalase are involved. Because of the toxicity of methanol, which is directly caused by its toxic metabolites, the major task in clinical toxicology is to inhibit each of these enzymes to protect human life. The aim of this investigation was to check the influence of some effective inhibitors of ADH and MEOS: 4-methylpyrazole, Cimetidine, EDTA and 1,10-phenantroline on the activity of catalase with methanol as a substrate and the comparison with 3-amino-1,2,4-triasole Catalase activity in rat hepatic homogenates was measured spectrophotometrically in vitro at physiological pH 7.4 and temp. 37 °С, assaying the degree of methanol oxidation according to Handler and Thurman. The quantity of arising formaldehyde was measured according with the method of Nash. Our results have shown that catalase activity was inhibited to different extents by all investigated compounds at concentrations of 10-3 mol/1, 2 x 10-4 mol/1, 10-4 mol/1, 2 x 10-5 mol/l, 10-5 mol/1. 1,10-Phenantroline was found to be a highly effective inhibitor in comparison with aminotriasole. 4-Methylpyrazole, EDTA, 1,10-phenantroline and aminotriasole are catalase competitive inhibitors and Cimetidine is non-competitive inhibitor. 4-Methylpyrazole has shown higher affinity to the enzyme than aminotriasole.

9

Influence of 30-day subacute intoxication with chlorfenvinphos and lead on some biochemical parameters in rats

80%

Maciejewska-Kozak H. , Dudka J. , Dawidek-Pietryka K. , Jeleniewicz K.

Acta Poloniae Toxicologica

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2001

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tom 09

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nr 2