Search results

1

Polymerization of Sickle Cell Disease and Methaeglobin in the Presence of Paracetamol

100%

Ihenetu S. C., Ikpa C. B. C., Igbokwe W. U., Okeke C. J., Ibe F. C.

World News of Natural Sciences

|

2022

|

vol. 43

96-107

EN

This study was designed to examine the Level of Polymerization of Sickle Cell Disease and Methaeglobin in the Presence of Paracetamol, the research was carried out using standard procedures. The present study has shown the level of polymerization of sickle cell disease and methaemoglobin in the presence of paracetamol. Within the experimental time of 30-180 seconds, the relative polymerizations range between the following; 70.43 ± 0.87 to 72.10 ± 0.37 at the control (0 mg/dl), at 50 mg/dl, there was an increase from 65.78 ± 0.89 to 69.47±1.00, at 100 mg/dl there was an increase in the polymerization from 68.96 ± 0.99 to 72.33 ±1.02, at 200 mg/dl there was an increase in the polymerization from 65.96 ± 69.26 ± 1.00 and at 500 mg/dl, there was an increase in the polymerization form 66.05 ± 0.98 to 69.42 ± 0.92. This increase in polymerization can be said to be due to the increase in the absorbance of paracetamol. However, the absorbance of the polymerization mixture in the presence of the malarial drug was not significantly different (p < 0.05) from the control sample at the 30 second. The present study showed that the level of polymerization of Hemoglobin S (HbS) molecules was attenuated upon the introduction of the anti-malarial drugs in the polymerizing mixture. The percentage of methaemoglobin increases with the increase in concentration of paracetamol from 2.77 ± 0.05 to 3.30 ± 0.03 starting from 0 mg/dl to 500 mg/dl concentration.

2

Analysis of cooperative interactions in molecularly imprinted polymer nanoparticles

100%

Mistry J., Guerreiro A., Moczko E., Piletska E., Karim K., Piletsky S. A.

Molecular Imprinting

|

2014

|

vol. 2

|

issue 1

EN

Cooperative binding is commonly observed in biological receptor systems. This study investigates whether it is possible to prepare nano-sized molecularly imprinted polymers (nanoMIPs) that show cooperative binding. NanoMIPs which exhibit cooperative binding would have increased affinity for immobilised template molecules making them useful for advanced applications in diagnostics and sensors. The use of a templatederivatised solid support provides a facile route to prepare nanoMIPs with surface imprints, and the method is ideally suited to study this topic. Although not observed during the course of this study, positive interbinding site cooperativity was hypothesised by way of an increase in the number of binding sites imprinted on the nanoMIPs, by increasing template density on the solid support surface. After synthesis, the affinity of nanoMIPs was analysed using surface plasmon resonance (SPR) technique. Under the conditions investigated, a ten fold increase in binding affinity was measured as template density was increased. SPR results could be explained by an increase in cooperative binding; however calculations showed that the increase in affinity was not significant enough to prove cooperative binding interactions. The main conclusion obtained was that MIP nanoparticles contain only one “high-affinity” binding site that interacts with immobilised template in an SPR assay.

3

DETERMINATION OF PARACETAMOL IN COMMERCIAL SUPPOSITORIES USING DIFFERENTIAL SCANNING CALORIMETRY

100%

Leyk E., Komar S., Wesołowski M.

Acta Poloniae Pharmaceutica - Drug Research

|

2019

|

vol. 76

|

issue 2

241-249

EN

Paracetamol, also known as acetaminophen, has been commonly used as a major active pharmaceutical ingredient in numerous analgesics for over 30 years. This means that specific and reliable methods are crucial for quality control of its formulations. The purpose of this work was to show to what extent differential scanning calorimetry (DSC) can be useful for the determination of paracetamol in formulations intended for rectal use. Suppositories commonly available in Polish pharmacies were chosen for the study. In order to assess the impact of various suppository bases on active ingredient determination in the formulations analyzed, the selection was made from various producers and with varying doses of paracetamol. DSC scans were taken on a heat-flux instrument with a liquid nitrogen cooling system. To achieve the aim of this study, a well-defined endothermic DSC peak was used, assigned to the melting-point of paracetamol at 168.64ºC with the heat of transition of 183.99 J/g. A multiple standard addition method was chosen for the calibration. Except for one formulation containing 50 mg of paracetamol, the relative standard deviation for all the DSC determinations varied over the range of 0.27 to 2.64%, while the relative error varied between 0.24 and 12.50%. The study demonstrated that DSC could successfully be employed as a simple, specific and reliable method for the determination of paracetamol in rectal preparations based on the measurement of its heat of fusion. The results are consistent with the data obtained using UV spectrophotometry (pharmacopoeial method) as reference.

4

The influence of single application of paracetamol and/or N-acetylcysteine on rats in subchronic exposition to trichloroethylene vapours. II. Effect on hepatic glutathione level

88%

Plewka D., Plewka A., Kowalówka-Zawieja J., Zielińska-Psuja B., Przystanowicz J.

Medycyna Środowiskowa - Environmental Medicine

|

2012

|

vol. 15

|

issue 3

91-95

EN

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.

PL

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.

5

The influence of single application of paracetamol and/or N-acetylcysteine on rats in subchronic exposition to trichloroethylene vapours. III. Effect on some isoforms of cytochrome P450 in liver

88%

Plewka A., Plewka D., Kowalówka-Zawieja J., Przystanowicz J., Zielińska-Psuja B.

Medycyna Środowiskowa - Environmental Medicine

|

2012

|

vol. 15

|

issue 4

24-30

EN

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 exposure.

PL

Wstęp: W przypadku przedawkowania paracetamolu, zdolność wątroby do detoksykacji zostaje wysycona i następuje akumulacja toksycznego metabolitu, jaki jest NAPQI. Główne izoformy CYP, uważane za odpowiedzialne za bioaktywację APAP-u i sprzyjające w ten sposób zatruciom wątrobowym, to CYP2E1, CYP1A2 oraz CYP3A4 a u zwierząt dodatkowo izoformy 2B1/2. Celem pracy było zbadanie wpływu paracetamolu i/lub trichloroetylenu na skład wątrobowych izoform cytochromu P450. Materiał i metody: Badania wykonano na szczurach, które traktowano trichloroetylenem, paracetamolem i/lub N-acetylocysteiną. We frakcji mikrosomalnej wątroby oznaczano zawartość trzech izoform cytochromu P450, tj., CYP2E1, CYP2B1/2 oraz CYP1A2. Wyniki: Paracetamol lekko stymulował CYP2E1 obniżając równocześnie poziom CYP1A2. Trichloroetylen stymulował CYP2B1/2. N-acetylocysteina miała stymulujący wpływ na wszystkie badane izoformy P450. N-acetylocysteina podawana łącznie z badanymi ksenobiotykami prowadziła do wyraźnych wzrostów CYP. Wnioski: N-acetylocysteina wykazywała ochronny wpływ na poziomy badanych izoform cytochromu P450, szczególnie, jeśli została podana zaraz po zaprzestaniu ekspozycji na ksenobiotyki.

6

The influence of single application of paracetamol and/or N-acetylcysteine on rats subchronic exposed to trichloroethylene vapours. I. Effect on hepatic moonooxygenase system dependent of cytochrome P450

88%

Plewka A., Plewka D., Przystanowicz J., Kowalówka-Zawieja J., Zielińska-Psuja B.

Medycyna Środowiskowa - Environmental Medicine

|

2012

|

vol. 15

|

issue 2

64-71

EN

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.

PL

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.

7

THE EFFECT OF A SINGLE OR MULTIPLE DOSES OF GRAPEFRUIT JUICE ON SOME PHARMACOKINETIC AND PHARMACODYNAMIC EFFECTS OF PARACETAMOL IN MICE

88%

AL ZA'ABI M., ALI B. H., AL-HDHRAMI A.

|

EN

Grapefruit juice (GFJ), a commonly consumed dietary substance, has been shown to alter the disposition of several commonly used drugs. The available data on the effects of GFJ on the paracetamol pharmacokinetics and pharmacodynamics are at variance. The aim of this study was to evaluate the effect of a single or multiple dose of GFJ on some pharmacokinetics and pharmacodynamics aspects of orally given paracetamol (400 mg/Kg). Male mice were randomly divided into three equal groups: mice in the first group were given paracetamol; the second group was given a single oral dose (10 mL/Kg) of GFJ one hour prior to paracetamol administration; the third group was administered multiple oral doses of GFJ (10 mL/Kg) for five consecutive days, and on the last day it was treated with paracetamol. Blood samples were collected 10, 20, 30, and 40 min, and 1, 2, 4, 6 and 8 h after paracetamol administration for subsequent pharmacokinetic analysis. Some mice in the same three groups were also tested for their reactions to thermal (hotplate) and chemical (acetic acid induced – abdominal constriction) nociceptive stimuli. GFJ increased the plasma concentration and area under the plasma concentration curve of paracetamol, to a greater extent after a single dose than multiple doses. It also increased the reaction time in the hotplate test, and reduced abdominal constrictions. GFJ administration increased the plasma concentration and the analgesic effect of paracetamol in mice. The possible implications of these changes in humans and their clinical relevance need to be further investigated.

8

VALIDATION OF HEPATOPROTECTIVE USE OF POLYGONUM PERFOLIATUM EXTRACT AGAINST PARACETAMOL INDUCED TOXICITY IN WISTAR RATS

75%

Saleem M., Mushtaq M. F., Akhtar M. F., Saleem A., Zahid S., Sharif A., Akhtar B., Dar E., Ullah M., Badshah M.

Acta Poloniae Pharmaceutica - Drug Research

|

2019

|

vol. 76

|

issue 2

283-289

EN

The liver as a vital body organ is adversely affected by hazardous chemicals and drugs. Paracetamol widely used as analgesic and antipyretic drug produces severe hepatotoxicity at high doses. Present study was designed to investigate the hepatoprotective activity of Polygonum perfoliatum L. used on folklore basis. Aqueous methanolic extract of the plant was prepared. Preliminary phytochemical and HPLC analyses were carried out to identify and quantify chemical constituents respectively. For hepatoprotective activity, Wistar rats were divided into six groups as normal control, standard (silymarin) control, negative control and extract treated groups i.e., 125, 250 and 500 mg/kg/day per oral. Paracetamol was administered orally, following seven days of previously stated therapy. Biochemical parameters of hepatotoxicity such as serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP) and total bilirubin were measured in all groups. Histopathological evaluation of liver was also carried out. Benzoic acid, chlorogenic acid, gallic acid, m-coumaric acid, quercetin and vitamin E were detected in the plant extract through HPLC. The hepatoprotective effect of 500 mg/kg/day therapy was more pronounced than 125 and 250 mg/kg dose. However, the effect of plant extract was less pronounced than standard silymarin therapy. It can be concluded that the plant extract possessed significant hepatoprotective activity that may be attributed to quercetin, benzoic acid, gallic acid and vitamin E present in it.

9

BIOAVAILABILITY OF DRUGS FROM SUPPOSITORIES IN CLINICAL PRACTICE AFTER 1995

75%

Hermann J., Hermann T. W.

Acta Poloniae Pharmaceutica - Drug Research

|

2020

|

vol. 77

|

issue 3

417-421

EN

Abstract: A review has been supposed to be arranged on the literature published between 1996 and 2018 concerning applications of suppositories in clinical practice. The rectal route of drug administration has been in use for centuries particularly in children, elderly and comatose patients as well as in palliative care and preterm infants undergoing painful procedures. Morphine, salbutamol, methadone, lidocaine, propranolol, theophylline, and mianserin, which allow to avoid the hepatic first-pass effect, are examples of preference of rectal route over oral one. Only two main classes of antibiotics (β-lactams and macrolides) have been studied recently after the rectal route of their administration. With the help of modern pharmaceutics and novel RDDS, higher bioavailability and controlled release of the drug have become possible. A number of antiepileptic drugs can be given rectally either for acute seizure control or in maintenance therapy. UC can be effectively treated with topical formulations and is superior to rectal corticosteroids. To suppositories most often used in Europe and the United States for their local treatments belong: bisacodyl, glycerol, mesalazine, diclofenac, glyceryl trinitrate, budesonide, prednisolone, and hydrocortisone. Suppositories applied for treatment of systemic conditions are more numerous.

10

Impairment in pain perception in adult rats treated with N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) as neonates

63%

Adamus-Sitkiewicz B., Kőrössy E., Bojanek K., Adwent M., Nowak P., Bałasz M., Kniaś M., Szkilnik R.

Annales Academiae Medicae Silesiensis

|

2009

|

vol. 63

|

issue 3

67-74

EN

BACKGROUND This study was designed to investigate the antinociceptive eff ect of morphine, paracetamol and nefopam in rats lesioned with DSP-4 as neonates. MATERIAL AND METHODS Intact male rats were contrasted with rats in which noradrenergic nerve terminals were largely destroyed shortly after birth with the neurotoxin DSP-4 [(N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg sc x2], on the 1st and 3rd days of postnatal life. When rats attained 10 weeks of age, painful reactions were assessed by means of tail immersion test and paw pressure test. Also monoamine levels in some part of the brain were estimated using HPLC/ED method. RESULTS AND CONCLUSION In the tail immersion test we showed that there are no diff erences between antinociceptive eff ect evoked by morphine (5.0 mg/kg sc) and paracetamol (100 mg/kg ip) between control and DSP-4 rats. Nefopam (20 mg/kg ip) elicited only slight analgesia in control rats (~ 17 %), this eff ect was no longer observed in the DSP-4 treated group. In the paw pressure test we demonstrated that morphine and paracetamol produced lower analgesia in DSP-4 rats in comparison to control. Nefopam evoked slight analgesia in both tested groups. In biochemical study we showed that in DSP-4 treated rats there was a marked decrease in NA level in the prefrontal cortex (to 10.4 %, p<0.01), thalamus with hypothalamus (to 54.4 %, p<0.05) and spinal cord (to 12.3 %, p<0.01) in comparison to the control group. Conversely, in the cerebellum and brain stem of DSP-4 lesioned rats there was a signifi cant increase in the NA content versus control (respectively to 171.2 % and 123.5 % of NA in controls, p<0.05). In the striatum we did not observe any changes in NA level between examined groups. Also the levels of 5-HT and its metabolite 5-HIAA were not altered by DSP-4 treatment in all tested structures with the exception of the spinal cord (approx. 40% decrease) and the level of DOPAC (also 40% reduction). In conclusion, the obtained results showed that neonatal DSP-4 treatment alters the antinociceptive eff ects of examined drugs (each of them with diff erent mechanism of action). These data lead to the proposal that perhaps there is a need to adjust the doses of analgetics applied to patients with noradrenergic system dysfunction (e.g. depression and/or anxiety disorders).

PL

W niniejszym eksperymencie oceniono wpływ lezji ośrodkowego układu noradrenergicznego wykonanej u noworodków szczurzych na przeciwbólowe efekty morfi ny, paracetamolu i nefopamu u dorosłych szczurów. MATERIAŁ I METODY 1-go i 3-go dnia życia noworodkom szczurzym podano neurotoksynę DSP-4 (50 mg/kg sc). Zwierzęta kontrolne otrzymały 0.9% roztwór NaCl (1.0 ml/kg sc). Po osiągnięciu wieku 10-ciu tygodni wykonano test imersji ogona oraz test wycofania łapy. Ponadto posługując się metodą HPLC/ED oznaczono zawartość amin biogennych i ich metabolitów w wybranych częściach mózgu badanych zwierząt. WYNIKI I WNIOSKI Nie stwierdzono różnicy w przeciwbólowym działaniu morfi ny (5.0 mg/kg sc) i paracetamolu (100 mg/kg ip) w teście imersji ogona pomiędzy grupą kontrolną i DSP-4, natomiast nefopam 20 mg/kg ip wywoływał słabszą analgezję u zwierząt DSP-4 w porównaniu do kontroli. Działanie przeciwbólowe morfi ny i paracetamolu w teście wycofania łapy było silniej wyrażone u szczurów kontrolnych w porównaniu do grupy DSP-4. Nie stwierdzono natomiast różnic w przeciwbólowych efektach nefopamu pomiędzy grupą kontrolną a DSP-4. DSP-4 stosowany 1 i 3-go dnia życia pozapłodowego spowodował istotny spadek zawartości NA w korze przedczołowej (do 10.4 %, p<0.005), wzgórzu z podwzgórzem (do 54.4 %, p<0.005) oraz w rdzeniu kręgowym (12.3 %, p<0.005) w porównaniu do kontroli. W móżdżku oraz w pniu mózgu u szczurów DSP- 4 obserwowano istotny wzrost zawartości NA (odpowiednio do 171.2 % i 123.5 % wartości NA u szczurów kontrolnych, p<0.005; p<0.05). W prążkowiu nie stwierdzono zmian zawartości NA. Podanie DSP-4 nie miało istotnego wpływu na zawartość 5-HT i jej metabolitu 5-HIAA oraz DA i jej metabolitów DOPAC oraz HVA we wszystkich badanych strukturach mózgu poza rdzeniem kręgowym. Na podstawie przeprowadzonych badań wyciągnięto wnioski, iż zniszczenie ośrodkowego układu noradrenergicznego zmienia przeciwbólowe efekty badanych analgetyków. Powyższe może pośrednio wskazywać na konieczność odpowiedniego dostosowania dawek tych leków u pacjentów z dysfunkcją ośrodkowego układu noradrenergicznego (np. u chorych z depresją lub zaburzeniami lękowymi).

11

Inflammatory and visceral pain perception in rats lesioned with DSP-4 as neonates

51%

Kőrössy E., Adamus-Sitkiewicz B., Nowak E., Bojanek K., Adwent M., Muchacki R., Bałasz M., Szkilnik R.

Annales Academiae Medicae Silesiensis

|

2009

|

vol. 63

|

issue 2

7-15

EN

BACKGROUND: The aim of this study was to examine the impact of the central noradrenergic lesion on the infl ammatory and visceral pain perception after morphine, paracetamol and nefopam administration. MATERIAL AND METHODS: Intact male rats were contrasted with rats in which noradrenergic system was destroyed with DSP-4; 50 mg/kg sc on the 1st and 3rd days of postnatal life. After 10 weeks, painful reactions were assessed by means of formalin and writhing test. Furthermore accumulation of L-dihydroxyphenlalanine (L-DOPA) and 5-hydroxytryptamine (5-HTP) in some parts of the brain were examined using HPLC/ED method. RESULT S : 30 min after morphine (5.0 mg/kg sc) challenge rats were injected into the right hind paw plantar surface with 50 μl 5% formalin solution. Both groups showed the typical biphasic nocifensive response curve lasting 60 min but DSP-4 lesioned rats scored more points in the fi rst and second phase as well as the interphase period than control group. After paracetamol (100 mg/kg ip) administration also typical biphasic nocifensive response curve were observed however no diff erences between control and DSP-4 treated rats were noticed. Similar results were obtained after nefopam (20 mg/kg ip) challenge. Injections of morphine evoked similar antinociception in visceral pain model in both tested groups (control and DSP-4). Paracetamol elicited lower analgesia in control than in DSP-4 rats while nefopam was without eff ect. In biochemical assay, applied analgesics modifi ed serotonin and dopamine synthesis rate but the eff ect (increase or decrease) depended on examined structure (the prefrontal cortex, thalamus with hypothalamus and brain stem). CONCLUSIONS: Obtained results demonstrated that DSP-4 treatment in rats modifi ed the antinociceptive eff ects of the analgetics with distinct pharmacological prosperities and mechanism of action. It is likely that similar nociception abnormalities may occur in patients with noradrenergic system dysfunction, so it points to the requirement of analgetics dosage adjustment.

PL

WSTĘP: Celem pracy było zbadanie wpływu lezji ośrodkowego układu noradrenergicznego na analgetyczne działanie morfi ny, paracetamolu i nefopamu u szczurów. MATERIAŁ I METODY: Noworodki szczurze 1-go i 3-go dnia życia otrzymały neurotoksynę DSP-4 (50 mg/kg sc) natomiast kontrola 0.9% roztwór NaCl (1.0 ml/kg sc). Po osiągnięciu wieku 10-ciu tygodni wykonano test formalinowy oraz wicia, oznaczono ponadto szybkość syntezy serotoniny i dopaminy w korze przedczołowej, wzgórzu z podwzgórzem oraz pniu mózgu metodą HPLC/ED. WYNIKI: W teście formalinowym stwierdzono, że obie grupy badawcze wykazywały typową dwufazową reakcję bólową trwającą 60 minut, nie mniej u zwierząt z lezją reakcja ta była znamiennie silniej wyrażona niż u kontroli. Takiej zależności nie stwierdzono po podaniu paracetamolu (100 mg/kg ip) lub nefopamu (20 mg/kg ip). W teście wicia wykazano, że efekty przeciwbólowego działania morfi ny nie różnią się pomiędzy badanymi grupami zwierząt. Paracetamol działał natomiast słabiej przeciwbólowo u kontroli niż w grupie DSP-4. Nefopam nie wykazywał efektu przeciwbólowego w teście wicia. W badaniach biochemicznych stwierdzono, że stosowane leki przeciwbólowe modyfi kują szybkość syntezy serotoniny i dopaminy ocenianą zawartością 5-hydroksytryptaminy (5-HTP) i L-dwuhydroksyfenyloalaniny (L-DOPA). Uzyskane efekty, tj. wzrost lub zmniejszenie syntezy uzależnione były od badanej struktury mózgu (kora przedczołowa, wzgórze z podwzgórzem, pień mózgu). WNIOSKI: Wyniki niniejszych badań wskazują, że uszkodzenie ośrodkowego układu noradrenergicznego wywołane podaniem DSP-4 we wczesnym okresie rozwoju osobniczego u szczurów w różny sposób modyfi kuje przeciwbólowe działanie analgetyków o odmiennym mechanizmie działania. Wydaje się, że podobne efekty mogą wystąpić u chorych z dysfunkcją układu noradrenergicznego, co może wskazywać na konieczność modyfi kacji dawek stosowanych leków przeciwbólowych.

Refine search results

Polymerization of Sickle Cell Disease and Methaeglobin in the Presence of Paracetamol

Analysis of cooperative interactions in molecularly imprinted polymer nanoparticles

DETERMINATION OF PARACETAMOL IN COMMERCIAL SUPPOSITORIES USING DIFFERENTIAL SCANNING CALORIMETRY

The influence of single application of paracetamol and/or N-acetylcysteine on rats in subchronic exposition to trichloroethylene vapours. II. Effect on hepatic glutathione level

The influence of single application of paracetamol and/or N-acetylcysteine on rats in subchronic exposition to trichloroethylene vapours. III. Effect on some isoforms of cytochrome P450 in liver

The influence of single application of paracetamol and/or N-acetylcysteine on rats subchronic exposed to trichloroethylene vapours. I. Effect on hepatic moonooxygenase system dependent of cytochrome P450

THE EFFECT OF A SINGLE OR MULTIPLE DOSES OF GRAPEFRUIT JUICE ON SOME PHARMACOKINETIC AND PHARMACODYNAMIC EFFECTS OF PARACETAMOL IN MICE

VALIDATION OF HEPATOPROTECTIVE USE OF POLYGONUM PERFOLIATUM EXTRACT AGAINST PARACETAMOL INDUCED TOXICITY IN WISTAR RATS

BIOAVAILABILITY OF DRUGS FROM SUPPOSITORIES IN CLINICAL PRACTICE AFTER 1995

Impairment in pain perception in adult rats treated with N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) as neonates

Inflammatory and visceral pain perception in rats lesioned with DSP-4 as neonates