The Protective Effect of Moringa oleifera Leaves Extract on Paracetamol Hepatotoxicity in Male Rats

In recent years, there has been an increase in concern regarding the effects of paracetamol poisoning on liver tissues, particularly when consumed in large amounts. Some studies have estimated that paracetamol is involved in 56% of acute liver diseases, whereas 0.4% of paracetamol overdose cases result in fatal-ity. In this study, the effects of Moringa oleifera on paracetamol toxicity in the liver were explored. It has been demonstrated that Moringa oleifera is highly nu-tritious, contains bioactive molecules, and is therapeutically beneficial. Many studies have shown that Moringa oleifera leaves possess a wide range of biologi-cal properties, including antioxidant, tissue protection, analgesic, antihyperten-sive, and immunomodulatory activities. This study highlights the protective role of Moringa oleifera on handling possible paracetamol hepatotoxicity in male rats. .

Cases Report of a Medication Error by Look-A-Like Packaging: Metoclopramide and Paracetamol Suppositories

Medication errors are Unlike adverse drug reactions (ADRs) or adverse drug events (ADEs);mistakes by healthcare personnel cause them. We reported two cases of developed symptoms of Metoclopramide over-dose. Metoclopramide was given as Paracetamol due to look-a-like packaging. In Emergency Departments, reviewing the patient’s medications to prevent look-a-like complications should be done for all patients with suspected drug toxicity.

Development and Evaluation of Stable Paracetamol Loaded Solid Dispersion with Enhanced Analgesic and Hepatoprotective Property

Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.

Effects of Sarcocephalus latifolius Fruits Extract on Paracetamol-Induced Liver Damage in Wistar Rats

Background and Aim: Sarcocephalus latifolius is a medicinal plant commonly used in traditional medicine to treat various diseases. The aim of the present study is to evaluate the hepatoprotective activity of Sarcocephalus latifolius fruits aqueous extract against paracetamol-induced liver damage in rats. Material and Methods: Aqueous extract of Sarcocephalus latifolius fruits at doses of 100, 250 and 500 mg/kg were administered orally to rats with paracetamol-induced hepatotoxicity (1 g/kg). The treatment with the extract and paracetamol lasted 7 days. Silymarin (50 mg/kg) was given as reference control. All tested drugs were administered orally. Results: Our results show that the Sarcocephalus latifolius fruits extract induced a significant reduction (p < 0.05) of serum enzymes alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (PAL) and total bilirubin (TB). Then, the extract at the dose of 500 mg/kg showed a better protection (p < 0.001) of hepatocytes with a percentage of protection of 43.59% ± 2.03%;59.43% ± 4.12%;73.29% ± 5.72% and 62.55% ± 7.48% for ALAT, ASAT, PAL and TB, respectively. The histology of livers exposed to paracetamol shows an inflammation of the hepatocytes. In addition, there was a significant alteration of the liver parenchyma. The 500 mg/kg extract showed a resorption of the inflammation. Histopathological examination showed that the extract regenerated paracetamol-induced liver damage. Conclusion: Aqueous extract of Sarcocephalus latifolius fruits has hepatoprotective activity against paracetamol-induced hepatotoxicity in rats. But it would be important to evaluate the activity of aqueous extract of Sarcocephalus latifolius fruits on oxidative stress parameters in vivo in rats. .

Investigation of hepatoprotective activity of Cyathea gigantea(Wall.ex.Hook.)leaves against paracetamol-induced hepatotoxicity in rats

Objective:To investigate the hepatoprotective activity of methanolic leaf extract of Cyathea gigantea(C.gigantea)against paracetamol induced liver damage in rats.Methods:The hepatoprotective activity for plant extract was investigated for paracetamol induced hepatoxicity in rats.Wislar albino rats of either sex were divided into five groups of 6 animals each and are given orally the following treatment for seven days.The normal control group was given 1%Na.CMC 1mL/kg bw,p.o.Paracetamol at dose of 1g/kg bw,p.o.was given as toxic dose for inducing hepatoloxicity.Silymarin(50mg/kg.p.o.) was given as reference standard.Two doses of C. gigantea extract i.e.,100 mg/kg.p.o.and 200 mg/kg,p.o.were tested for hepatoprotective activity. The treatment was given for seven days and after 24 h of last treatment blood was collected from retro-orbital plexus and analysed for various serum parameters like serum glutamic-oxaloacetic transaminase(SGOT),serum glutamic pyruvic transaminase(SGPT),alkaline phosphatase(ALP),total bilirubin(TB)and total protein(TP)in different groups.Results:The paracetamol intoxication lead to histological and biochemical deteriorations.The treatment with methanolic leaf extract of C.gigantea reduced the elevated levels of SCOT,SGPT,ALP,TB and also reversed the hepatic damage towards normal which further supports the hepatoprotective activity of leaf extract of C.gigantea.Conclusions:The methanolic extract of leaves of C.gigantea at doses of 100 mg/kg bw and 200 mg/kg bw have significant effect on liver of paracetamol induced hepatotoxicity model in rats.

Hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatocellular damage in Wistar albino rats

Objective:To evaluate the hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatic damage in rats.Methods:The plant material was shade dried, powdered and extracted with ethanol.Liv 52 and silymarin were used as standard drugs and 2%gum acacia as a control(vehicle).Alteration in the levels of biochemical markers of hepatic damage like AST,ALT,ALP and lipid peroxides were tested,and phytochemical tests were also performed.Results:Paracetamol(2 g/kg) increased the serum levels of alanine aminotransfer (ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP) and the lipid peroxides. Treatment of Liv 52,silymarin and ethanolic extract of Terminalia paniculata(200 mg/kg) altered levels of biochemical marker and showed significant hepatoprotective activity.Ethanolic extract revealed the presence of phenolic compound and flavanoids.Our findings suggested that ethanolic bark extract of Terminalia paniculata possessed hepatoprotective activity in a dose dependent manner.Conclusions:Terminalia paniculata possesses hepatoprotective activity.It could be an effective and promising preventive agent against PCT induced hepatotoxicity.

Quantification of theophylline or paracetamol in milk matrices by high-performance liquid chromatography

A simple, accurate and sensitive high-performance liquid chromatography （HPLC） method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method allowed drug quantification in fresh and powdered milk with a relatively short run time of analysis and it was also successfully applied to the quantification of the drugs in solid dosage forms intended for pediatric use. Moreover, the main significant advantages over other published works are the simplicity of the sample preparation, reduced assay time and sample loss. The method meets the International Conference on Harmonization guideline for analytical methods validation regarding specificity, linearity, accuracy, precision, specificity and robustness as required by health authorities and applied by industry while designing and marketing new drug products. The technique encompasses the separation of the analytes with a reverse phase C18 column under isocrafic conditions and UV detection at 272 nm and 243 nm, respectively, for theophylline and paraeetamol. The lower limit of quantification for both drugs was determined as 0.2 μg/mL and the between-batch accuracy was 99.7%. This HPLC method allows quantification of theophylline and paracetamol in milk matrices and it can be applied in the design, development and production of milk-based pediatric dosage forms.

Liver injury induced by paracetamol and challenges associated with intentional and unintentional use

Drug induced liver injury(DILI)is a common cause of acute liver injury.Paracetamol,also known as acetaminophen,is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels.Hepatotoxicity from paracetamol overdose,whether intentional or nonintentional,is the most common cause of DILI in the United States and remains a global issue.Given the increased prevalence of combination medications in the form of pain relievers and antihistamines,paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity,as evidenced by its contribution to over half of all acute liver failure cases in the United States.This is especially concerning given that,when co-ingested with other medications,the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy.This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.

Hepatoprotective effect of leaf extracts from Citrus hystrix and C.maxima against paracetamol induced liver injury in rats

The present investigation is aimed to evaluate the hepatoprotective effects of Citrus hystrix and Citrus maxima(Red and White variety)methanolic leaf extracts on paracetamol induced toxicity.Leaf extracts were given in the dose of 200 mg/kg body weight for 7 days and toxicity was induced by paracetamol(2 g/kg)on day 5.Silymarin(100 mg/kg body weight)was used as reference standard.On the 7th day animals were sacrificed and liver function markers(ALT,AST,ALP),total bilirubin and total protein in blood serums and hepatic antioxidants(SOD,CAT,GSH and GPx)in liver homogenate were estimated.The leaf extracts restored the liver function markers and hepatic antioxidants to the normal level than elevated levels noticed on paracetamol control at P<0.001.Reversal of hepatoarchitecture has also been registered.The present study shows that C.hystrix and C.maxima leaf extracts possess hepatoprotective action against paracetamol induced hepatotoxicity.©2015 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Simultaneous Quantification of Ibuprofen and Paracetamol in Tablet Formulations Using Transmission Fourier Transform Infrared Spectroscopy

A very simple, non-destructive, inexpensive and green strategy was applied for the simultaneous determination of ibu-profen (IBP) and paracetamol (PC) using transmission Fourier Transform Infrared (FTIR) spectroscopy in tablet formulations for routine quality control laboratories. For the determination of the active pharmaceutical ingredients (API), KBr pellets containing known amount of standards and samples were used for acquisition of the FTIR spectra. The partial least squares (PLS) calibration model was developed using the spectral region from 1781 - 1683 cm-1 for IBP and 1630 - 1530 cm-1 for PC. The excellent coefficients of determination (R2), 0.9999 and 0.9998 were achieved for IBP and PC, respectively. The accuracy of calibration model was also verified through root mean square error of cross validation (RMSECV) which was found to be 0.064. This work clearly shows the capability of transmission FTIR spectroscopy for assessment of exact quantity of API to control the quality of finished products as well as during processing in pharmaceutical industries without involvement of any solvent.

Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and dif erential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution proi les. The dissolution parameters of the 1:4 batch was faster with- m∞(90.5%), t50%(3.5 min), t70%(11.6 min) while that of ratio 1:1 was the least with- m∞(48.6%), m5min(23.8%). Their release kinetics followed a KorsmeyerPeppas model with a super case-II transport mechanism.Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specii cations. The t50% value of the 1:4 batch of tablets may i nd its usefulness in formulating drugs for which a fast onset of action is desired.

Long-term administration of large doses of paracetamol impairs the reproductive competence of male rats

Aim: To evaluate the antireproductive effect of paracetamol in male rats. Methods: Male rats were orally adminis-tered daily with 500 mg/kg or 1000 mg/kg of paracetamol for 30 consecutive days. Their sexual behaviour and fertilitywere evaluated using receptive females. Results: At 2 h after treratment, sexual behaviour was not inhibited but onday 30 both doses of paracetamol caused marked impairment of libido (assessed by % mounting, % intromission and% ejaculation), sexual vigour (number of mounts and intromissions and copulatory efficiency) or sexual performance(intercopulatory interval). In mating experiments, the fertility (in terms of quantal pregnancy, fertility index, implan-tation index and number of implants) was significantly reduced. All these effects were reversible. The antireproductiveeffect was not due to a general toxicity but due to an increase in pre-implantation losses resulting from oligozoospermia,impairments of normal and hyper-activated sperm motility, and reduction in the fertilizing potential of spermatozoa.Conclusion: Long-term use of high doses of paracetamol may be detrimental to male reproductive competence.( Asian J Andro12000 Dec; 2: 247-255 )

Development of a microcomposite with single-walled carbon nanotubes and Nd_2O_3 for determination of paracetamol in pharmaceutical dosage by adsorptive voltammetry

This study presents for the first time a new composite of carbon paste(CP), single-walled carbon nanotubes(SWCNTs) and Nd2 O3(NdOX). This versatile composite(NdOX-SWCNT/CPE) was applied to the oxidation of paracetamol(PCM). The newly formed surface was characterized by scanning electron microscopy(SEM), electrochemical impedance spectroscopy(EIS) and cyclic voltammetry(CV). The results showed greater conductivity and a higher surface area for the composite than those of the carbon paste alone. Moreover, the anodic peak currents for PCM increased from 1.6 to 3.6 m A with CPE and NdOXSWCNT/CPE, indicating an increase of nearly 51.0% for the anodic peak current. On the other hand, the anodic peak potentials shifted from 0.67 to 0.57 V. The detection limits were 0.05 mmol/L with NdOXSWCNT/CPE and 0.50 mmol/L with SWCNT/CPE. The relative standard deviations(RSDs) were 1.5%(n=7). The accuracy and interference of the methods were evaluated with a urine chemistry control spiked with known quantities of PCM, uric acid, dopamine, ascorbic acid, caffeine, acetylsalicylic acid,tartrazine, sunset yellow, allure red, rutin, morin and metal ions. Finally, the novelty and usefulness of the composite were evaluated to quantify PCM in pharmaceutical dosage forms such as tablets, powders and syrups for children.

Nitrogen-doped carbon@TiO_(2) double-shelled hollow spheres as an electrochemical sensor for simultaneous determination of dopamine and paracetamol in human serum and saliva

As the most commonly used antipyretic and analgesic drug,paracetamol(PA)coexists with neurotransmitter dopamine(DA)in real biological samples.Their simultaneous determination is extremely important for human health,but they also interfere with each other.In order to improve the conductivity,adsorption affinity,sensitivity,and selectivity of TiO_(2)-based electrochemical sensor,N-doped carbon@-TiO_(2) double-shelled hollow sphere(HeC/N@TiO_(2))is designed and synthesized by simple alcoholic and hydrothermal method,using polystyrene sphere(PS)as a template.Meanwhile,TiO_(2) hollow spheres(H eTiO_(2))or N-doped carbon hollow spheres(HeC/N)are also prepared by the same method.HeC/N@TiO_(2) has good conductivity,charge separation,and the highly enhanced and stable current responses for the detection of PA and DA.The detection limit and linear range are 50.0 nmol/L and 0.3-50 mmol/L for PA,40.0 nmol/L and 0.3e50 mmol/L for DA,respectively,which are better than those of carbon-based sensors.Moreover,this electrochemical sensor,with high selectivity,strong anti-interference,high reliability,and long time durability,can be used for the simultaneous detection of PA and DA in human blood serum and saliva.The high electrochemical performance of HeC/N@TiO_(2) is attributed to the multifunctional combination of different layers,because of good conductivity,absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO_(2).

Analgesic effect of paracetamol combined with low- dose morphine versus morphine alone on patients with biliary colic： a double blind, randomized controlled trial

BACKGROUND:Numerous drugs have been proposed to alleviate pain in patients with biliary colic,especially opioids,but still there is a tendency to use less narcotics because of their side effects and the unwillingness of some patients.The present study aimed to compare the analgesic effect of paracetamol combined with low-dose morphine versus morphine alone in patients with biliary colic.METHODS:A randomized double-blind controlled trial was performed in 98 patients with biliary colic,recruited from two emergency departments from August 2012 to August 2013.Eleven patients were excluded and the remaining were randomized into two groups:group A received 0.05mg/kg morphine+1 000 mg paracetamol in 100 m L normal saline and group B received 0.1 mg/kg morphine+normal saline(100 m L)as placebo.Pain scores were recorded using visual analogue scale(VAS)at baseline and 15 and 30 minutes after drug administration.Adverse effects and the need for rescue medication(0.75 g/kg intravenous fentanyl)were also reported within 60 minutes of drug administration.RESULTS:Before the infusion,the mean±SD VAS scores were 8.73±1.57 in group A and8.53±1.99 in group B.At 15 minutes after drug administration,the mean±SD VAS scores were2.16±1.90 in group A vs.2.51±1.86 in group B;mean difference was–0.35,and 95%CI–1.15 to 0.45(P=0.38).At 30 minutes the mean±SD VAS scores were 1.66±1.59 in group A vs.2.14±1.79 in group B;mean difference was–0.48,and 95%CI–1.20 to 0.24(P=0.19).The mean pain scores in the two groups at 15 and 30 minutes demonstrated no significant difference.CONCLUSION:Paracetamol combined with low-dose morphine may be effective for pain management in patients with biliary colic.

Hepatoprotection: A Hallmark of <i>Citrullus colocynthis</i>L. against Paracetamol Induced Hepatotoxicity in Swiss Albino Rats

Objective: To demonstrate the in-vivo hepatoprotective effect of the ethanolic extracts of Citrullus colocynthis (Linn.) against paracetamol induced hepatotoxicity in albino rats. Animal Model: Swiss Albino rats of either sex were used, divided into six groups with six in each group. Group 1-Normal control: The animals were maintained under normal control, which were given distilled water only. Group 2-Induction of hepatotoxicity: The animals received paracetamol 500 mg/kg b.w. (p.o) every 72 h for 10 Days. Groups 3 to 5: Animals received ethanolic extract of Citrullus colocynthis L. at 50, 100 & 200 mg/kg bw/day for 7 days (p.o). Group 6: The animals were treated with Silymarin (100 mg/kg p.o) which served as standard. Groups 3 to 6 were intoxicated with paracetamol (500 mg/kg bw) 1 h before the administration of extract or Silymarin for 10 days. Histopathological findings, different hepatic biochemical parameters viz. AST, ALT, ALP, Total bilirubin, Total cholesterol, Triglycerides, & the body weight before & after treatment were evaluated to investigate the hepatoprotective activity. Results: Paracetamol induced a significant rise in AST, ALT, ALP, Total Bilirubin, Total Cholesterol, Triglycerides. Administration of 200 mg/kg bw of ethanolic extract of Citrullus colocynthis L. effectively reduced these pathological damages caused by paracetamol intoxication. In addition to serum parameters treatment of 200 mg/kg bw of ethanolic extract of Citrulus colocynthis L. also promotes the body weight in albino rats as shown in Figure 6 respectively. Histopathological changes of the liver samples were compared with the normal control as shown in Figures 2-5 respectively. Conclusion: From our results we may infer that the mode of action of 90% ethanolic extract of Citrullus colocynthis L. (200 mg/kg bw) in affording the in-vivo hepatoprotective activity against paracetamol may be due to the cell membrane stabilization, hepatic cell regeneration & normalizing the serum parameters.

DFT Cancer Energy Barrier and Spectral Studies of Aspirin, Paracetamol and Some Analogues

Comparative DFT computations were studied between Paracetamol (PA) and its analogues such as p-nitroace- tanilide (PA-NO2), p-bromoacetanilide (PA-Br) and N-acetylanthranilic acid (NAA) which can be considered also as analogue of Aspirin (ASP). As well, Thio-Aspirin, Acetyl-Thio-Salicylic acid, (TASP) is another analogue of ASP. From DFT studies, it has been concluded that PA and its analogues have the predominant trans-conformers with respect to directions of the carbonyl group in the acetyl moiety and the amino-hydrogen atom but the predominant conformer of NAA molecule is the cis-form. Phenacetin (PH) molecule which has ethoxy group in the Para-position instead of the hydroxyl group in the Para-position in PA molecule is another analogue of PA. The electron transfer energy between the drugs and the nucleic acid bases can be illustrated as cancer energy barrier. The cancer energy barriers were calculated from the DFT parameters for all the studied molecules showing the carcinogenic effect. The metabolized product N-acetylimidoquinone, m-PA, is produced in the liver from PA and PH. m-PA has higher electron affinity more than those of the nucleic acid bases indicating to the strong electronic withdrawing power from the nucleus in the human being liver cell, hence m-PA is responsible for the carcinogenic behavior of the liver cell since it has low energy barrier with guanine, 0.3 eV. Therefore the electron transfer between m-PA and guanine takes place spontaneously in the liver. From CI calculations it has been concluded that the singlet transition energies for the trans and cis conformers of PA are the same. The comparative spectral studies have been scanned for some analogues in the visible and UV regions using solvents of different polarities. The complex between PA and Zn2+ was studied by DFT method.

Pain on Injection of Propofol: Efficacy of Paracetamol and Lidocaine

Background and Objectives: Propofol remains the most common drug for induction of general anaesthesia, although it causes considerable pain on injection. None of the commonly used methods completely attenuate this discomfort. We aimed to investigate the effect of i.v. paracetamol pretreatment on the propofol injection pain. Materials and Methods: A prospective randomized double-blind study was conducted on 180 patients, ASA I or II status, scheduled to undergo elective surgery. They were randomly assigned to one of the three groups of 60 each. Groups I, II, III were pretreated with 40 mg of lidocaine in saline, 100 mg of paracetamol and 10 ml of saline, respectively. All patients had an 18-gauge catheter inserted into a superficial radial vein. After 2 min of venous occlusion, one-fourth of the total propofol dose was injected into the vein over a period of 20 seconds. During the injection of both pretreatment solution and propofol, a blinded researcher assessed the patient’s pain level using a four-point verbal rating scale (VRS) (none = 0, mild = 1, moderate = 2, and severe = 3). X2 test and Kruskal-Wallis tests were used for the statistical analysis. For all analyses, differences were considered to be significant at P < 0.05. Results: The three groups were comparable in respect to patient’s characteristics. The incidence of pain on injection of propofol in placebo, i.v. paracetamol and lidocaine groups were 85%, 36%, 21% respectively (p < 0.05). Intensity and severity of propofol induced pain were comparable between paracetamol and lidocaine groups. Conclusion: Pretreatment using i.v. paracetamol was found to be effective in reducing propofol injection-induced pain.

Water/Oil Pickering Emulsion Stabilized by Magnesium Oxide Particles: A Potential System with Two Active Substances (Paracetamol and Griseofulvin)

Pickering emulsions are systems without surfactants, stabilized by solid particles. These emulsions are experiencing a renewed interest, on the one hand, because it is preferable to limit the use of synthetic surfactants for toxicological and environmental reasons and, on the other hand, the need to make new formulations in order to control the drug release patterns by encapsulation or controlled release. Thus, we were interested in the formulation and evaluation of W/O Pickering emulsions stabilized by particles of magnesium oxide with paracetamol in the internal phase and griseofulvin in the external phase. The Bancroft rule served as a model for the formulation. The emulsification was carried out by progressively adding an aqueous phase dispersed in an oil-dispersing phase using a turbo rotor stator mixer. The stability of these emulsions was studied using several parameters (droplet size, pH, viscosity, conductivity ...) and the qualitative and quantitative analysis of the active ingredients by UV-visible spectrophotometry. The results obtained showed that the dye test and the conductivity measurement confirmed the W/O nature of these emulsions. Some parameters such as droplet size, pH and viscosity were strongly influenced by the amounts of magnesium oxide particles and the two active ingredients used. The qualitative and quantitative analysis of the active ingredients confirmed the presence of griseofulvin in the oil phase and paracetamol in the aqueous phase. Thus, we have succeeded in developing a stable W/O Pickering emulsion with magnesium oxide particles. In addition, we were able to incorporate paracetamol into the dispersed phase and griseofulvin into the dispersing phase of the emulsion.

Amelioration of paracetamol hepatotoxicity and oxidative stress on mice liver with silymarin and Nigella sativa extract supplements

Objective: To evaluate the ameliorator property of silymarin or/and Nigella sativa(N. sativa) extract against N-acetyl-p-aminophenol(APAP)-induced injury in male mice at the biochemical, histological and ultrastructural levels.Methods: The mice were divided into seven groups(10/group). The first group was served as control. While, the second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa extract alone respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa extract respectively. The seventh group was treated with combination of both ameliorative compounds(silymarin and N. sativa extract) with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose to mice led to an alteration of liver functions, increased the alanine transaminase, aspartate aminotransferase and lactate dehydrogenase levels, decreased total protein level as well as the increasing the superoxide dismutase and malondialdehyde while decreased catalase, glutathione peroxidase and glutathione reduced activities. The effects of APAP on the biochemical parameters of mice were dose-dependent. Administration of silymarin or/and N. sativa extract to APAP-treated mice attenuates the toxicity of this compound, objectified by biochemical, histological and ultrastructural improvement of liver. But the alleviation was more pronounced with the both antioxidants. Conclusions: The synergistic effect of silymarin and N. sativa extract is the most powerful in reducing the toxicity induced by APAP and improving the liver functions and antioxidant capacities of mice.