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. .

Preparation of Cetyl-Chitosan Nanoparticles as Carriers for Paracetamol

Cetyl-chitosan, prepared by reacting chitosan with chlorocetane under alkaline condition, is soluble and spontaneously forms nanoparticles about 100 nm in diameter. Infrared spectra (IR) revealed that there was a substitution reaction mainly on the amine groups of chitosan (CS). By using paracetamol (PCTM) as a model drug, the balanced release concentration of PCTM in phosphate buffer solution (pH=7.4) can be decreased with the increase of degree of substitution alkyl and can be reduced effectively even under a lower PCTM loading.

Elimination of NAPQI, the Toxic Metabolite of Paraceta-mol, by Ebselen

Ebselen. 2-phenyl-1, 2-benzisoselenazol-3 (2H)-one, activated by. glutathione(GSH) was shown to react with N-acetyl-p-benzoquinone imine (NAPQI). the toxic rnetabolite ofparacetamol, but not to react with paracetamol. The GSH-activaled ebselen reacts uith NAPQI fasterand more complete than with ebselen alone. Compared xvith the UV-spectra of the solution containing20 μmol/L ebselen tactivated by 20 pmol/L GSH) and 20 pmol/L NAPQI with the solution contain-ing 20 μmol/L ebselen tactivated by 20 μmol/LGSH) and 20 μmol/L paracetamol, NAPQI was foundto be reduced to paracetamol by activated ebselen. The optimal PH range for this reaction was foundto be 7.4 to 8.2.

Hypothetical mode of action of earthworm extract with hepatoprotective and antioxidant properties

The hepatoprotective potential of earthworm extract (EE) (Lampito mauritii, Kinberg) was evaluated against paracetamol-induced liver injury in Wistar albino rat, in comparison with silymarin, the standard hepatoprotective drug. We observed a reduction in liver antioxidants, such as glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) and in serum total protein, and an increase in serum alkaline phosphatase (ALP), serum aspertate aminotranferase (AST), serum alanine aminotranferase (ALT), bilirubin and liver thiobarbituric acid reactive substances (TBARS) due to liver injury in the paracetamol-administered rats (2 g/kg). On the contrary, increased activities of liver GSH, SOD, GPx, CAT and serum total protein level, and decrease in the contents of serum ALP, AST, ALT, bilirubin and liver TBARS were observed in rats administered with different doses of EE (100, 200 and 300 mg/kg), which are similar to the activities of hepato-protective drug silymarin (150 mg/kg). The mode of action of EE as evidenced by the above parameters may suggest that EE, on the one hand, prevents the formation of the reactive oxygen groups, or scavenges these groups, thereby preventing the damage on the hepatic cells, and, on the other hand, modulates the genes responsible for synthesis of antioxidant enzymes such as GPx, CAT and SOD in liver tissue and decreases the serum enzymatic activities such as ALP, AST and ALT.

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.

Hepatoprotective activity of Hepax-A polyherbal formulation

Objective:To evaluate the hepatoprotective potential of Hepax,a polyherbal formulation,against three experimentally induced hepatotoxicity models in rats.Methods:Hepatoprotective activity of Hepax was studied against three experimentally induced hepatotoxicity models,namely, carbon tetrachloride(CCl_4),paracetamol and thiocetamide induced hepatotoxicity in rats. Results:Administration of hepatotoxins(CCl_4,paracetamol and thiocetamide) showed significant morphological,biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with Hepax had significant protection against hepatic damage by maintaining the morphological parameters(liver weight and liver weight to organ weight ratio) within normal range and normalizing the elevated levels of biochemical parameters(SGPT,SCOT,ALP and total bilirubin),which were evidently showed in histopathological study.Conclusions:The Hepax has highly significant hepatoprotective effect at 100 and 200 mg/kg,p.o.on the liver of all the three experimental animal models.

Oral pharmacological treatment for patent ductus arteriosus in premature neonates with hemodynamic repercussions

Objective: To evaluate the efficacy of oral indomethacin, ibuprofen, and paracetamol in oral dosage form on patent ductus arteriosus(PDA) in premature neonates with significant clinical and hemodynamic repercussions(CHRs) and to determine the effect of these respective treatments on renal function.Methods: A retrospective study of cases of PDA in premature neonates in the Neonatal Intensive Care Unit was conducted. The treatments consisted of indomethacin[0.2 mg/(kg$d), 3-day cycle], ibuprofen [10 mg/(kg$d) followed by 5 mg/(kg$d), 3-day cycle], and paracetamol(15 mg/kg every 6 h, 5-day cycle). The drugs were administered as an oral solution. The following variables were considered: gestational age,newborn weight at birth, Apgar score, diuresis, serum creatinine and urea levels, and serum electrolyte levels(sodium and potassium).Results: Treatment with indomethacin presented efficacy of 87.5% in closure of the ductus with a mean outcome period of 3.5 d. In premature neonates with CHRs and contraindications for indomethacin, the initial treatment with either ibuprofen or paracetamol failed to close the ductus. However, when this treatment was followed by indomethacin, closure occurred in 66.7% of the neonates, with an outcome period of9.66 d. The initial treatment with one cycle of ibuprofen followed by one or two cycles of paracetamol failed to close the ductus.Conclusions: Oral indomethacin was effective for closure of the PDA in premature neonates with severe CHRs. Oral paracetamol or ibuprofen for PDA closure in premature neonates with severe CHRs and contraindications for indomethacin was ineffective.However, results in clinical improvements of neonates allowed the subsequent use of indomethacin and successful closure of the ductus. A significant reduction of diuresis occurred in neonates who were treated with indomethacin, either as a first-line treatment or after the failure of ibuprofen or paracetamol.

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.

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.

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.

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.

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.

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.

Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus

Patent ductus arteriosus(PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects.

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).

Epidemiology and outcomes of acute liver failure in Australia

BACKGROUND Acute liver failure (ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain. AIM To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia. METHODS The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults (> 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival (OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988- 2001. RESULTS Paracetamol was the most common aetiology of acute liver failure, accounting for 50% of cases, with an increased incidence compared with the historical cohort (P = 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival (TFS) improved significantly compared to the historical cohort (52% vs 38%, P = 0.032). TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF (P < 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients (25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and 72% respectively. CONCLUSION Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.

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.