Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes (β-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α2-noradrenergic (yohimbine), β-adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride). The results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly (p < 0.05) reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly (p < 0.05) inhibited by (i) antagonists of μ-, δ-, and κ-opioid receptors; (ii) antagonists of α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and (iii) blockers of different K+ channels (voltage-activated-, Ca2+-activated, and ATP-sensitive-K+ channels, resp.). In conclusion, MECN-induced antinociception involves modulation of protein kinase C-, bradykinin-, TRVP1 receptors-, and glutamatergic-signaling pathways; opioidergic, α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and nonopioidergic receptors as well as the opening of various K+ channels. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds.
Matched MeSH terms: Analgesics, Non-Narcotic/therapeutic use
Acetaminophen overdose may be accompanied by electrolyte disturbances. The basis for electrolyte change appears to be due to increased fractional urinary electrolyte excretion.
Intravenous N-acetylcysteine is usually regarded as a safe antidote. However, during the infusion of the loading dose, different types of adverse drug reactions (ADR) may occur. The objective of this study was to investigate the relation between the incidence of different types of ADR and serum acetaminophen concentration in patients presenting to the hospital with acetaminophen overdose. This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (1 January 2004 to 31 December 2008). Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Of 305 patients with acetaminophen overdose, 146 (47.9%) were treated with intravenous N-acetylcysteine and 139 (45.6%) were included in this study. Different types of ADR were observed in 94 (67.6%) patients. Low serum acetaminophen concentrations were significantly associated with cutaneous anaphylactoid reactions but not other types of ADR. Low serum acetaminophen concentration was significantly associated with flushing (p < 0.001), rash (p < 0.001) and pruritus (p < 0.001). However, there were no significant differences in serum acetaminophen concentrations between patients with and without the following ADR: gastrointestinal reactions (p = 0.77), respiratory reactions (p = 0.96), central nervous reactions (p = 0.82) and cardiovascular reactions (p = 0.37). In conclusion, low serum acetaminophen concentrations were associated with higher cutaneous anaphylactoid reactions. Such high serum acetaminophen concentrations may be protective against N-acetylcysteine-induced cutaneous ADR.
Acetaminophen is one of the most commonly encountered medications in self-poisoning, with a high rate of morbidity. The prevalence and characteristics of acetaminophen intoxication associated with long hospital stay in patients are not well defined.
Intravenous N-acetylcysteine (IV-NAC) is widely recognized as the antidote of choice for acetaminophen overdose. However, its use is not without adverse drug reactions (ADR) that might affect therapeutic outcome or lead to treatment delay.
In the presence of hydroxyl and amine groups, chitosan is highly reactive; therefore, it could be used as a carrier in drug delivery. For this study, chitosan-Sm complexes with different concentrations of samarium from 2.5 to 25 wt.% have been successfully synthesized by the impregnation method. Chitosan combined with Sm3+ ions produced a drug carrier material with fluorescence properties; thus, it could also be used as an indicator of drug release with ibuprofen (IBU) as a model drug. We evaluated the spectroscopic and interaction properties of chitosan and Sm3+ ions, the interaction of chitosan-Sm matrices with IBU as a model drug, and the effect of Sm3+ ions addition on the chitosan ability to adsorb the drug. The result showed that the hypersensitive fluorescence intensity of chitosan-Sm (2.5 wt.%) is higher than the others, even though the adsorption efficiency of chitosan-Sm 2.5wt.% is lower (29.75%) than that of chitosan-Sm 25 wt.% (33.04%). Chitosan-Sm 25 wt.% showed the highest efficiency of adsorption of ibuprofen (33.04%). In the release process of ibuprofen from the chitosan-Sm-IBU matrix, the intensity of orange fluorescent properties in the hypersensitive peak of 4G5/2→6H7/2 transition at 590 nm was observed. Fluorescent intensity increased with the cumulative amount of IBU released; therefore, the release of IBU from the Sm-modified chitosan complex can be monitored by the changes in fluorescent intensity.
In the present study, a nanocomposite of f-MWCNTs-chitosan-Co was prepared by the immobilization of Co(II) on f-MWCNTs-chitosan by a self-assembly method and used for the quantitative determination of paracetamol (PR). The composite was characterized by field emission scanning electron microscopy (FESEM) and energy dispersive x-ray analysis (EDX). The electroactivity of cobalt immobilized on f-MWCNTs-chitosan was assessed during the electro-oxidation of paracetamol. The prepared GCE modified f-MWCNTs/CTS-Co showed strong electrocatalytic activity towards the oxidation of PR. The electrochemical performances were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Under favorable experimental conditions, differential pulse voltammetry showed a linear dynamic range between 0.1 and 400 μmol L-1 with a detection limit of 0.01 μmol L-1 for the PR solution. The fabricated sensor exhibited significant selectivity towards PR detection. The fabricated sensor was successfully applied for the determination of PR in commercial tablets and human serum sample.
Pharmacological and biochemical studies on the Ammi majus seeds L. (family Umbelliferae) grown in Egypt are limited. Furocoumarins are the major constituents in the plant seeds. In the present study, the evaluation of the antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities on albino rats and mice was done. After 2 months of administration, both the doses (50 and 100 mg/kg body weight [bwt], respectively) of the alcoholic extract of the A. majus seed result in a significant decrease in the concentrations of cholesterol, triglycerides, and low-density lipoprotein and increase in the concentration of high-density lipoprotein. The extract was found to inhibit the rat paw edema at both the doses, which means that it exerts a significant anti-inflammatory activity compared with control-untreated groups at the intervals of 30 and 60 minutes posttreatment. The antipyretic effect of the extract was quite obvious; it showed that 100 mg/kg bwt was more potent in lowering body temperature starting after 1 hour of treatment than the lower dose (50 mg/kg bwt). It is worth to mention that the A. majus extract with its coumarin contents as well as the tested biological activities of the plant was investigated for the first time in the current study. In conclusion, ethanolic extract of the A. majus seeds had antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities that are dose dependant.
Moringa oleifera Lam. (Moringaceae) is a rich source of essential minerals and antioxidants; it has been used in human and animal nutrition. The leaves and flowers are being used by the population with great dietary importance.
The anti-pyretic activity of a standardized methanol/water (50/50) extract of Orthosiphon stamineus Benth. (SEOS) was investigated for its effect on normal body temperature and yeast-induced pyrexia in Sprague Dawley (SD) rats. The SEOS showed no effect on normal body temperature. Doses of 500 and 1000 mg/kg body weight of SEOS significantly reduced the yeast-induced elevation in body temperature. This effect persisted up to 4 h following the administration of the extract. The anti-pyretic effect of SEOS was comparable with that of paracetamol (acetaminophen in U.S) (150 mg/kg p.o.), a standard anti-pyretic agent. HPLC study revealed that rosmarinic acid, sinensetin, eupatorin and tetramethoxyflavone were present in SEOS in the amounts of 7.58%, 0.2%, 0.34% and 0.24% respectively. The LD(50) of the extract in rats was higher than 5000 mg/kg body weight. Therefore, the present study ascertained that SEOS possesses a significant anti-pyretic activity.
During recent years, there has been growing interest in the use of nanoemulsion as a drug-carrier system for topical delivery. A nanoemulsion is a transparent mixture of oil, surfactant and water with a very low viscosity, usually the product of its high water content. The present study investigated the modification of nanoemulsions with different hydrocolloid gums, to enhanced drug delivery of ibuprofen. The in vitro characterization of the initial and modified nanoemulsions was also studied.
Two hundred and ninety five children admitted with acute gastroenteritis from January 1, 1996 to December 31, 1996 to the Paediatric unit, University of Malaya Medical Centre, Kuala Lumpur, were reviewed. Eighty-nine percent of children received treatment before admission. Information regarding the type of treatment received were available in 152 (52%) cases. Eighty percent of them were prescribed medications, 40% were prescribed glucose-electrolyte mixtures, and 13% were advised a change of formula. Only 18 children (12%) were advised to take glucose-electrolyte mixtures alone. The four most common prescribed drugs were: antibiotics (43%), antipyretics (39%), antidiarrhoeal agents (30%), and antiemetics (24%). The use of antibiotics, antiemetics and antidiarrhoeal drugs for children with acute gastroenteritis among primary care doctors appears to be common. The use of glucose-electrolyte mixtures was uncommon.
Matched MeSH terms: Analgesics, Non-Narcotic/therapeutic use
It is generally accepted that the tablet elastic relaxation during compaction plays a vital role in undermining the final tablet mechanical integrity. One of the least investigated stages of the compaction process is the ejection stage.
Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.
The present study was carried out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of the aqueous extract of Melastoma malabathricum leaves in experimental animals. The antinociceptive activity was measured using abdominal constriction, hot-plate, and formalin tests, whereas the anti-inflammatory and antipyretic activities were measured using carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. The extract, which was obtained after soaking the air-dried leaves in distilled water for 72 h and then preparing in concentrations of 10%, 50%, and 100% (v/v), was administered subcutaneously 30 min prior to subjection to the above mentioned assays. At all concentrations tested, the extract was found to exhibit significant (P < 0.05) antinociceptive, anti-inflammatory, and antipyretic activities in a concentration-independent manner. Our findings that the aqueous extract of M. malabathricum possesses antinociceptive, anti-inflammatory, and antipyretic activities supports previous claims on its traditional uses to treat various ailments.
Because durian (Durio zibethinus), which is known in Southeast Asia as "the king of fruits", is thought to have special body-warming properties, it should not be consumed with paracetamol due to a risk of toxic effects. The claim of warming properties, however, has not been scientifically proven. This study was conducted to investigate durian's hyperthermic effect and its toxicity when consumed together with paracetamol in rats. Five groups of rats (n=6) were fed with: 1) distilled water (4 ml/250 g), 2) homogenized durian (4 g/250 g), 3) paracetamol solution (2400 mg/kg), 4) durian (4 g/250 g) followed by paracetamol solution (2400 mg/kg), or 5) prazosin solution (15 mg/kg, pregavaged) followed 1 h later by durian (4 g/250 g) and paracetamol solution (2400 mg/kg). Rectal temperature, systolic blood pressure and serum alanine aminotransferase (ALT) levels were taken from each rat at baseline and after the various administrations at 1, 2 and 5 h. Our results showed that the body temperature of rats in the durian-treated group was not significantly elevated when compared to the control. However, there was a significant decrease in body temperature over time in animals from groups 4 and 5. We did not, however, observe a consistent pattern of blood pressure change. Serum chemical analysis for ALT also did not show any significant change in any of the groups. In conclusion, contrary to what some believe, even though durian was found to increase body temperature in some rats, this increment was not significant. Rats receiving the durian-paracetamol combination showed a significant drop in body temperature, which may explain the belief that the two mixtures are toxic. However, the exact mechanism of toxicity is still unknown.
This study was performed to determine the antinociceptive and anti-inflammatory activities of aqueous extract of Kaempferia galanga leaves using various animal models. The extract, in the doses of 30, 100, and 300 mg/kg, was prepared by soaking (1:10; w/v) the air-dried powdered leaves (40 g) in distilled water (dH(2)O) for 72 h and administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot-plate and formalin tests, with activity observed in all tests occurring in a dose-dependent manner. Furthermore, the antinociceptive activity of K. galanga extract was significantly (P < 0.05) reversed when prechallenged with 10 mg/kg naloxone. The extract also produced a significantly (P < 0.05) dose-dependent anti-inflammatory activity when assessed using the carrageenan-induced paw-edema test. In conclusion, this study demonstrated that K. galanga leaves possessed antinociceptive and anti-inflammatory activities and thus supports the Malay's traditional uses of the plant for treatments of mouth ulcer, headache, sore throat, etc.
BACKGROUND: Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration.
RESULTS: Group-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p < 0.05. Hepatic histopathology showed vascular congestion in group-B; mild congestion in group-C (but lesser than in group-B and D). In group-D, at low doses of sunitinib, lesser damage than in group-B occurred but larger changes including congestion were observed at high sunitinib doses. BUN levels were higher (p < 0.05) for group-B (33.81 ± 5.68 mg/dL) and group-D (range 35.01 ± 6.95 U/L to 52.85 ± 12.53 U/L) compared to group-A (15.60 ± 2.17 mg/dL) and group-C (range 17.50 ± 1.25 U/L to 26.68 ± 6.05 U/L). Creatinine remained unchanged. Renal congestion and necrosis was lower in group-C than group-B but was higher in group-D (p > 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs.
CONCLUSIONS: Paracetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended.