11 research outputs found
Influence of acetylsalicylic acid on hematotoxicity of benzene
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 conentration 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). Results: Benzene 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. Conclusion: Our results suggest that ASA limited the benzene-induced hematotoxicity
Influence of acetylsalicylic acid on hematotoxicity of benzene
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 conentration 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). Results: Benzene 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. Conclusion: Our results suggest that ASA limited the benzene-induced hematotoxicity
Wpływ pojedynczej dawki paracetamolu i/lub N-acetylocysteiny na szczury przewlekle eksponowane na trichloroetylen. I. Wpływ na wątrobowy układ monooksygenaz zależnych od cytochromu P450
Background: There is a number of factors which
potentially affect occurrence of toxic change in liver
after overdosing of paracetamol. Hepatic metabolism
of trichloroethylene has primary impact on hepatotoxic
effect of this solvent. This means that the combined
exposure to these xenobiotics can be particularly harmful
for human. The influence of N-acetylcysteine (NAC)
as a protective factor after paracetamol intoxication
was studies.
Materials and method: Tests were carried out on rats
which were treated with trichloroethylene, paracetamol
and/or N-acetylcysteine. In the hepatic microsomal fraction
activity of the components of cytochrome P450-
dependent monooxygenases was determined
Results: Paracetamol slightly stimulated cytochrome
P450 having no effect on reductase activity cooperating
with it. Cytochrome b5 and its reductase were inhibited
by this compound. Trichloroethylene was the inhibitor
of compounds of II microsomal electron transport
chain. N-acetylcysteine inhibited activity of reductase
of NADH-cytochrome b5.
Conclusions: Tested doses of the xenobiotics influenced
on II microsomal electron transport chain. Protective
influence of N-acetylcysteine was better if this
compound was applied 2 hours after exposure on xenobiotics.Wstęp: Istnieje szereg czynników, które potencjalnie
wpływają na ryzyko wystąpienia zmian toksycznych
w wątrobie po przedawkowaniu paracetamolu. Wątrobowy
metabolizm trichloroetylenu ma pierwszorzędny
wpływ na hepatotoksyczny efekt tego rozpuszczalnika.
Oznacza to, że narażenie łączne na te ksenobiotyki
może być szczególnie szkodliwe dla człowieka. Oceniono
wpływ N-acetylocysteiny (NAC) jako czynnika osłaniającego
po zatruciu paracetamolem. Materiał i metody: Badania wykonano na szczurach,
które traktowano trichloroetylenem, paracetamolem
i/lub N-acetylocysteiną. We frakcji mikrosomalnej wątroby
oznaczano aktywność składników monooksygenaz
zależnych od cytochromu P450.
Wyniki: Paracetamol lekko stymulował cytochrom
P450 nie mając wpływu na aktywność reduktazy współpracującej
z nim. Cytochrom b5 i jego reduktaza były
hamowane przez ten związek. Trichloroetylen był inhibitorem
składników II mikrosomalnego łańcucha transportu
elektronów. N-acetylocysteina hamowała aktywność
reduktazy NADH-cytochrom b5.
Wnioski: Badane dawki ocenianych ksenobiotyków
swój wpływ ujawniały raczej na składniki II mikrosomalnego
łańcucha transportu elektronów. Ochronny
wpływ N-acetylocysteiny był wyraźniejszy, jeśli podano
ten związek 2 godziny po zakończeniu ekspozycji
na badane ksenobiotyki
New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs)
The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st–3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted
Wpływ pojedynczej dawki paracetamolu i/lub N-acetylocysteiny na szczury przewlekle eksponowane na trichloroetylen. II. Wpływ na wątrobowy poziom glutationu
Background: Feature of modern existing hazards
both environmental and occupational is cumulative
exposure often leading to unexpected response of the
organism resulting, among other things, in interactions
with cytochrome P450 system involved in biotransformation
of trichloroethylene and paracetamol. Hepatotoxity
of paracetamol is closely connected with hepatic
glutathione level. „In therapy of acute paracetamol poisoning
application of N-acetylcysteine as a factor, which
protects GSH level in cells, is recommended.”
Materials and method: Tests were performed on rats
which were treated with trichloroethylene, paracetamol
and/or N-acetylcysteine. In rat liver total level of glutathione
was determined i.e. reduced and oxidized form.
Results: Paracetamol just after completion of the
exposure affected the glutathione level. Trichloroethylene
throughout the period of observation stimulated
growth of glutathione level in liver. N-acetylcysteine
didn’t have any influence on the level of investigated
tripeptyde.
Conclusions: N-acetylcysteine removes negative
effect of paracetamol especially when it’s applied with
2-hour delay. After exposure for trichloethylene immediate
application of N-acetylcysteine caused noticeable
lowering of glutathione level. Cumulative exposure for
three xenobiotics had positive influence for glutathione
level in rat liver.Wstęp: Cechą współcześnie występujących zagrożeń,
zarówno środowiskowych jak i zawodowych jest narażenie
łączne, wielokrotnie prowadzące do nieprzewidzianej
odpowiedzi biologicznej organizmu, wynikającej między innymi z oddziaływań na układ cytochromu
P450 biorący udział w biotransformacji trichloroetylenu
i paracetamolu. Hepatotoksyczność paracetamolu jest
między innymi ściśle związana z wątrobowym poziomem
glutationu. W terapii zatruć ostrych paracetamolem
zalecane jest podawanie N-acetylocysteiny jako
czynnika ochraniającego poziom GSH w komórkach.
Materiał i metody: Badania wykonano na szczurach,
które traktowano trichloroetylenem, paracetamolem
i/lub N-acetylocysteiną. W wątrobie szczura oznaczano
poziom całkowity glutationu, tj. formę zredukowaną
i utlenioną.
Wyniki: Paracetamol tuż po zakończeniu ekspozycji
negatywnie wpływał na poziom glutationu. Trichloroetylen
przez cały czas obserwacji stymulował wzrost poziomu
glutationu w wątrobie. N-acetylocysteina nie miała
żadnego wpływu na poziom badanego tripeptydu.
Wnioski: N-acetylocysteina usuwała negatywny
wpływ paracetamolu, szczególnie wtedy, kiedy podano
ją z 2-godzinnym opóźnieniem. Po narażeniu na trichloroetylen
natychmiastowe podanie N-acetylocysteiny
niosło za sobą wyraźnie obniżenie poziomu glutationu.
Narażenie łączne na trzy oceniane ksenobiotyki
Wpływ pojedynczej dawki paracetamolu i/lub N-acetylocysteiny na szczury przewlekle eksponowane na trichloroetylen. III. Wpływ na wybrane izoformy cytochromu P450 w wątrobie
Background: In case of overdose of paracetamol the
ability of hepatic biotransformation is saturated and accumulation
of toxic metabolite – NAPQI takes place. Main
CYP isoforms considered to be responsible for bioactivation
of APAP and promoting the same liver intoxication are
CYP2E1, CYP1A2, CYP3A4 and in animals 2B1/2 isoforms
additionally. Purpose of this work was examination of
paracetamol influence and/or trichloroethylene on the
composition of hepatic cytochrome P450 isoforms. Materials
and method: Tests were carried out on rats which
were treated with trichloroethylene, paracetamol and/or
N-acetylcysteine. In the microsomal fraction content of
three isoforms of cytochrome P450 i.e. CYP2E1, CYP2B1/2
and CYP1A2 were determined. Results: Paracetamol slightly
stimulated CYP2B1/2 lowering simultaneously level of
CYP1A2. Trichloroethylene stimulated CYP2B1/2. N-acetylcysteine
stimulated all tested P450 isoforms. N-acetylcysteine
given together with examinated xenobiotics induced
studied P450 isoforms. Conclusions: N-acetylcysteine
demonstrated a protective effect on studied CYP isoforms
especially when was given upon termination of xenobiotics
exposur
Causes of Death during the Intravenous Infusion of Dimethylsulphoxide and Hydrogen Peroxide in the Course of Alternative Medicine Therapy
Unconventional (alternative, natural) medicine in Poland and worldwide includes hundreds of non-scientifically verified “treatment” modalities. Among the most popular are biological therapies using chemical or natural compounds administered with injection or drip infusion. The latter has found the most excellent use in treating rheumatological and dermatological diseases and certain types of cancer. Vitamin infusions, curcumin, glutathione, perhydrol and dimethylsulphoxide (DMSO) have gained popularity among clients of natural medicine clinics. The present study aims to analyse the case of a 37-year-old woman who was administered infusions containing perhydrol and DMSO (0.5 mL 0.04% hydrogen peroxide/0.5 mL p.d.a DMSO in saline) due to a MTHFR A1298C mutation. After having the next infusion, the woman complained of nausea and then became unconscious. Subsequently, she suffered respiratory and cardiac arrest. Adequate resuscitation was undertaken. After being taken to the hospital, the patient was in critical condition and died due to increasing multiple-organ failure. Initially, there was suspected DMSO poisoning as it was the only compound to have been administered as an intravenous infusion. However, it was not until the analysis of the secured evidence that it became clear that the patient had also been given an intravenous solution of hydrogen peroxide, H2O2, and that there had been a mistake in preparing the intravenous perhydrol solution. The autopsy concluded that the immediate cause of death was an acute cardiopulmonary failure due to the toxic effects of intravenously administered hydrogen peroxide. This conclusion was established after the toxicological testing of the evidence and biological material secured during the patient’s treatment and autopsy. Products containing DMSO and perhydrol are not included in the lists of medicinal/therapeutical forms and preparations and thus are not authorised for marketing in Poland. In the case of perhydrol, apart from the topical use of diluted preparations for washing and cleansing wounds, no data on therapeutic use exist in the available scientific literature. Furthermore, “DMSO and perhydrol therapy” cannot even be considered a placebo effect, as both are toxic compounds which could, at most, cause poisoning symptoms rather than improve health
Influence of acetaminophen and trichloroethylene on liver cytochrome P450-dependent monooxygenase system.
The aim of the study was to evaluate the effect of acetaminophen (APAP) and/or trichloroethylene (TRI) on the liver cytochrome P450-dependent monooxygenase system, CYP2E1 and CYP1A2 (two important P450 isoforms), and liver glutathione (GSH) content in rats. Rats were given three different doses of APAP (250, 500 and 1000 mg/kg b...) and then the above-mentioned parameters were measured for 48 h. The lowest APAP dose produced small changes in the cytochrome P450 content of liver. At 500 mg/kg APAP increased the cytochrome P450 content to 230% of the control. The inductive effect was seen at 1000 mg/kg dose but at 24 h and later. NADPH-cytochrome P450 reductase activity was the highest after the lowest dose of APAP, while after the highest dose it was equal to the control value. TRI increased both the cytochrome P450 content and the NADPH-cytochrome P450 reductase activity. When TRI was combined with APAP, both these parameters increased in the first hours of observation, but they returned to the control values at 24 h. When APAP was given at 250 mg/kg, GSH levels decreased to 55% of the control at 8 h and returned to the control values at 24 h. The higher doses of APAP decreased GSH levels more than the lowest dose, but after 24 h GSH levels did not differ from those of the control. When TRI was given at 250 mg/kg, the GSH levels decreased to 68% of the control at 2 h and then they increased gradually and tended to exceed the control values at 48 h. The effect of TRI combined with APAP on the level of GSH was virtually the same as that of APAP alone given at 500 mg/kg