Paracetamol In Rats Research Articles

The protective role of ascorbic acid on the testis tissue damage induced by paracetamol in albino rats

Ascorbic acid (AA) plays roles in many biological functions, such as participating in the production of collagen by taking a role in proline and lysine hydroxylation. AA works by removing the reactive oxygen species, thus removing the adhesion of neutrophils to endothelium. The present study investigates the protective effects of AA on the testis tissue damage induced by paracetamol in rats. Thirty-two male rats were equally divided into four groups, with eight rats in each. Group (1) regular control group, group (2) was received 500 mg/kg/b.w. of AA orally for two weeks, group (3) was received 500 mg/kg/b.w. of paracetamol orally for two weeks, group (4) was treated with the AA (500 mg/kg/b.w.) and paracetamol (500 mg/kg/b.w.) orally for two weeks. The histopathological investigations of the testis tissues from the paracetamol group showed atrophy and degeneration of seminiferous tubules with an absence of spermatozoa, presence of cell debris, and loss of the Sertoli cells in some seminiferous tubules when compared with control animals. The testis tissues from a protective group showed less damage in the tubules and germ cells when compared with the paracetamol group. This study indicates that AA protects against paracetamol-induced testis damage in adult male rats.

A validated LC-MS/MS bioanalytical method for the pharmacokinetic interaction study of the effect of some co-administered COVID-19 protocol drugs on pholcodine containing antitussive mixture

The symptoms of the viral infection COVID-19, which range from mild to severe, can include fever, coughing, sore throats, malaise, headaches, and a loss of taste or smell. Fever and cough are the most typical symptoms of COVID-19, and in more severe cases, it can make breathing difficult. Hence, in this in-vivo study, we studied the effect of the simultaneous co-administration of COVID-19 treatment drugs (azithromycin, dexamethasone, and hydroxychloroquine) on the pharmacokinetics of the antitussive drugs combination: pholcodine, pseudoephedrine and paracetamol in rats. For the simultaneous determination of pholcodine, pseudoephedrine, and paracetamol in rat plasma, a UPLC-MS/MS technique was developed and approved. a mobile phase made up of 0.15% aqueous formic acid: acetonitrile (20:80, v/v) was used using an Xterra C18 MS column (3.5 m, 4.6 × 50 mm). The detection procedure involved the employment of a multiple reaction monitoring mode utilizing triple-quadrupole tandem mass spectrometer. The concentration range for pholcodine, pseudoephedrine, and paracetamol was linear across 12–1000 ng/ml, 10–550 ng/ml, and 400–30000 ng/ mL, respectively. The results show that the coefficient of variation is satisfactory at quality control samples for all the mentioned drugs, confirming the accuracy and precision of the method. This approach was successfully implemented in a rat drug-drug pharmacokinetic interaction study to determine whether the co-administration of COVID-19 protocol medications would affect the bioavailability of pholcodine, pseudoephedrine and paracetamol. It was found that azithromycin, dexamethasone, and hydroxychloroquine co-administration significantly affect the bioavailability of these drugs, increasing their systemic exposure as a result and this could potentially lead to increasing adverse effects. Therefore, healthcare professionals should consider the potential drug-drug interaction when prescribing these medications to COVID-19 patients.

Chlorzoxazone reduced the paracetamol-induced toxicity via competitive inhibition of CYP2E1-mediated metabolism

BackgroundDrug metabolism is crucial to attaining the therapeutic index of any drug. The metabolism and elimination of the drugs are governed mainly by P-glycoprotein (P-gp) and Cytochrome P450 (CYP). Paracetamol is mostly used as analgesic and antipyretic agent. The metabolism of paracetamol is primarily via Glucuronidation and sulphation at therapeutic doses. About 5–10% of paracetamol is metabolized via CYP mediated pathway. Cytochrome P450 2E1 (CYP2E1) is primarily responsible for forming a toxic metabolite of paracetamol called N-acetyl-p-benzoquinoneimine (NAPQI). Even at therapeutic doses, long-term usage of paracetamol leads to the hepatic and nephrotoxicity because of NAPQI. Several in-vitro and in-vivo studies conducted by different research groups and reported that chlorzoxazone is a substrate and inhibitor of CYP2E1. However, the effect of chlorzoxazone on the paracetamol (CYP2E1 substrate) metabolism via the CYP2E1 has not yet been reported. This study investigated the effect of chlorzoxazone on the CYP2E1-mediated metabolism of Paracetamol and NAPQI formation in Wistar rats.ResultsFor 15 days, animals were orally administered with Paracetamol (300 mg/kg) with and without Silymarin (100 mg/kg) (standard CYP2E1 inhibitor) and Chlorzoxazone (50 and 100 mg/kg). Analysis was performed using RP-HPLC on the 15th day to determine paracetamol and NAPQI concentration in the plasma. Paracetamol combination with chlorzoxazone (50 and 100 mg/kg) showed a dose-dependent increase in the AUC0–∞ and the peak plasma concentration (Cmax) of Paracetamol and a dose-dependent decrease of AUC0–∞ and Cmax of NAPQI compared to paracetamol control (p < 0.001). Chlorzoxazone significantly decreased the elevated liver and renal markers compared to paracetamol control. Simultaneously, Hepatic and nephrotic tissue studies showed that compared to the paracetamol control group, the combination of chlorzoxazone significantly ameliorated paracetamol-induced hepatotoxicity and nephrotoxicity.ConclusionFinally, this study revealed that paracetamol in combination with chlorzoxazone led to a significant decrease in the plasma levels of NAPQI and enhanced absorption of paracetamol in rats via the inhibition of CYP2E1- mediated metabolism. In addition, chlorzoxazone significantly ameliorated paracetamol-induced hepatotoxicity and nephrotoxicity.

Influence of biologically active substance Darmonal and phytin compounds on the liver functional state at experimental hepatitis caused by paracetamol

The study aimed to investigate the protective mechanisms of substance Darmonal and phytin compounds in the experimental model of acute toxic drug-induced hepatitis caused by paracetamol in rats. The material and methods The research was carried out on white outbred rats of both sexes weighing 140-200 g. Drug-induced liver damage was reproduced by introduction of paracetamol into the stomach in dose 500 mg/kg for 2 days. The test compounds Darmonal, Fitin-C and reference drug Liv.52 were administered for 7 days after hepatitis reproduction in doses 100 mg/kg. The effectiveness and mechanism of action for selected supramolecular complexes in the model of toxic drug-induced hepatitis was made by paracetamol. It was researched that liver protein-synthesizing function was due to the content of total protein and albumin in the blood serum, the excretory and toxic function of the liver by the content of total and direct bilirubin as well as the endogenous intoxication were according to the content of urea in the blood serum, but cytolytic syndrome occurred because of the activity of indicator enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood serum). Research results. The study of specific activity of Darmonal in combination with Fitin-C and the reference drug Liv.52 on the model of paracetamol and carbon tetrachloride hepatitis showed that the drugs, being administered in dose 100 mg/kg, had a pronounced hepatoprotective effect.

Nephroprotective Activity of an Aqueous Extract of Alchornea Cordifolia Stapf. (Euphorbiaceae) on Acute Kidney Injury Induced by Paracetamol in Rat

Nephroprotective Activity of an Aqueous Extract of Alchornea Cordifolia Stapf. (Euphorbiaceae) on Acute Kidney Injury Induced by Paracetamol in Rat

Effect of Taraxacum officinale L. ethanol extract against kidney injuries induced by paracetamol in rats

Background/Aim: The biochemical effects of dandelion (D) ethanol extract on blood and renal tissue in rats induced by paracetamol (PRC) were examined in this study. Methods: In this study was utilized 36 Sprague Dawley male rats, aged 5 months. Rats were divided 6 groups of 6 rats each, randomly. Control group (C), D200 group, D250 group, PRC group, PRC+D200 group, PRC+D250 group, was given orally per os (p.o) in a single dosage (2 g/kg/b.w.) and dandelion extract (200-250 mg/kg) was given intraperitoneally (i.p) for 8 days. Results PRC raised plasma levels of urea, uric acid, and creatinine, as well as malondialdehyde, nitrate, and nitrite in kidney tissue. Furthermore, antioxidant levels/activities in renal tissue were reduced. Dandelion reduced plasma levels of urea, uric acid, and creatinine, as well as lipid peroxidation, nitrat, and nitrit in kidney tissue, while simultaneously increasing antioxidant activities. Conclusion: In this study was investigated that dandelion ethanol extract can be used excellent protection against PRC damage.

Effect of Taraxacum officinale L. ethanol extract against kidney injuries induced by paracetamol in rats

Effect of Taraxacum officinale L. ethanol extract against kidney injuries induced by paracetamol in rats

Histopathological study on the protective effect of vitamin C against paracetamol-induced acute hepatic damage in rat.

Paracetamol (PCM) as analgesic drugs makes hepatotoxicity damage. Vitamin C (VC) has been recognized as an antioxidant and has shown protective effects against hepatotoxicity damage caused by paracetamol. The current investigation aims to study the possible protective effects of VC against hepatic damage induced by PCM in rats. Forty male rats were divided into five groups: The primary group as control; receiving distilled water orally, the second group; receiving 500 mg/kg of VC. The third group; receiving 500 mg/kg of PCM. The fourth group (protective group); receiving VC for 7 days, and then PCM for another 7 days, and the last group treated with a combination of VC and PCM for 14 days. The liver tissues after administration of PCM alone showed different changes such as disrupted lobular architecture with degenerating hepatocytes, dilated congested central vein, and mononuclear cellular infiltration. While the protective group preserved the general architecture and lacked evidence of major morphological. Additionally, VC with PCM showed some alterations in the liver architecture. In conclusion, the results of this study demonstrate that VC was effective in reducing the hepatic damage caused by PCM in male albino rats.

Punica. Granatum peel ethanol extract may exhibit liver protection activity against hepatotoxicity induced by paracetamol in rats

Punica. Granatum peel ethanol extract may exhibit liver protection activity against hepatotoxicity induced by paracetamol in rats

Liposomal coenzyme Q10 abates inflammation, apoptosis and DNA damage induced by an overdose of paracetamol in rat's liver

ObjectivesParacetamol (PCM) is widely used for its pain-relieving and antipyretic properties. However, acute intoxication of PCM remains one of the most common causes of drug-induced hepatic failure. A comparative study is conducted to evaluate the effectiveness of coenzyme Q10 (CoQ10) with that of liposomal CoQ10 (L-CoQ10) against PCM-induced liver injury. MethodAcute liver injury was induced by a single oral dose of PCM (1000 mg/kg). CoQ10 and L-CoQ10 treatments were given orally (10 mg/kg), 1 and 12 h following PCM intoxication. Specific oxidative stress, inflammatory and apoptotic biomarkers were measured, and then proved by histopathological examination. ResultsPCM administered rats exhibited a remarkable increase in the levels of serum aminotransferase enzymes, as well as hepatic interleukin-6, C-reactive protein, malondialdehyde (MDA) and nitric oxide (NO); whereas reduced glutathione (GSH) level and superoxide dismutase (SOD) activity were decreased. BAX, Nuclear factor-kappa B (NF-κB) and cytochrome C were overexpressed, while BCL-2 was downregulated. The results of the previous parameters were supported by histopathological study of liver tissue. Using either CoQ10 or L-CoQ10 caused a significant reduction of oxidative stress by enhancing GSH and SOD activity levels and diminishing MDA and NO levels. Moreover, both CoQ10 and CoQ10 caused downregulation of pro-inflammatory cytokines and BAX, and upregulation BCL-2, and these effects mostly noticed in L-CoQ10 treated rats. Likewise, rats receiving L-CoQ10 exhibited restoration of normal hepatic architecture. ConclusionL-CoQ10 supplement is useful for counteracting the hepatotoxicity induced by PCM overdose, via reducing the oxidative stress, inflammation and apoptosis.

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats

PurposeSorafenib is a multi-targeted tyrosine kinase inhibitor (TKI) used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. Neoplastic diseases are the cause of pain, which may occur regardless of the stage of the disease. Paracetamol is a non-opioid analgesic used alone or in combination with opioids for the treatment of cancer pain. Numerous studies have pointed out changes in the pharmacokinetic parameters of TKIs when co-administered with paracetamol. The aim of the study was to assess drug–drug interactions (DDIs) between sorafenib and paracetamol.MethodsRats were divided into three groups, each consisting of eight animals. The first group received sorafenib (IIS), the second group received sorafenib + paracetamol (IS+PA), whereas the third group received only paracetamol (IIIPA). A single dose of sorafenib (100 mg/kg b.w.) and paracetamol (100 mg/kg b.w.) was administered orally. The plasma concentrations of sorafenib and its metabolite–N-oxide as well as paracetamol and its glucuronide and sulphate metabolites were measured using validated high-performance liquid chromatography (HPLC) method with ultraviolet detection.ResultsThe co-administration of sorafenib and paracetamol increased the maximum concentration (Cmax) of paracetamol by 33% (p = 0.0372). In the IS+ PA group the Cmax of paracetamol glucuronide was reduced by 48% (p = < 0.0001), whereas the Cmax of paracetamol sulphate was higher by 153% (p = 0.0012) than in the IIIPA group. Paracetamol increased sorafenib and sorafenib N-oxide Cmax by 60% (p = 0.0068) and 83% (p = 0.0023), respectively.ConclusionsA greater knowledge of DDI between sorafenib and paracetamol may help adjust dose properly and avoid toxicity effects in individual patients.

CHRONOPHARMACOLOGICAL FEATURES OF SILIMARIN’S HEPATOPROTECTOCAL ACTIVITY UNDER PARACETAMOL HEPATITIS IN RATS

Determination of dependence of the efficiency and toxicity of drugs on the time of day or season is one of the most promising areas of modern experimental and clinical pharmacology. The aim of the study. Aim is to identify features of daily rhythms of silymarin influence on the state of antioxidant/prooxidant and cytolytic processes (the leading link in the implementation of hepatoprotective activity) with paracetamol in rats under conditions of acute toxic liver damage. Materials and methods. Chronopharmacological action features of silymarin were studied by use of the generic drug "Karsil" as an example (Sopharma, Bulgaria) with paracetamol in rats under conditions of acute toxic liver damage. The state of the processes of POL-AOS was evaluated by the content of TBA-active products (TBA-AP), the content of recovered glutathione, the activity of SOD, catalase in hepatocytes, and the cytolytic processes by the activity of ALT in serum. Results. There was established a certain chronoarchitectonics of the rhythms of the antioxidant protection system and the activity of the processes of peroxidation in rats under physiological conditions, which was not disturbed by paracetamol on the background of acute liver damage (with the exception of level of acrophase catalase activity). The same dynamics and commonality of rhythms occurred on the background of the use of silymarin. The maximum display of silymarin hepatoprotective activity was observed under conditions of its use in the morning (09.00) and in the evening (21.00). Conclusions. The use of silymarin during periods of maximal display of its hepatoprotective activity, in the morning (09.00) and in the evening (21.00) may be the way to increase its bioavailability. Chronopharmacological features of silymarin activity have been established and should be taken into account when to conduct its further chronopharmacological studies.

Hepatoprotective Activity of Leucas cephalotes against Paracetamol induced Hepatotoxicity in Rats

The present study was conducted to evaluate the hepatoprotective activity of ethanolic extract of Leucas cephalotes against Paracetamol induced liver damage in rats. The ethanolic extract of Leucas cephalotes (600mg/kg) was administered orally to the animals with hepatotoxicity induced by Paracetamol (3gm/kg). Silymarin (25mg/kg) was given as reference standard. All the test drugs were administered orally by suspending in 0.5% Carboxy methyl cellulose solution. The plant extract was effective in protecting the liver against the injury induced by Paracetamol in rats. This was evident from significant reduction in serum enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin. It was concluded from the result that the ethanolic extract of Leucas cephalotes possesses hepatoprotective activity against Paracetamol induced hepatotoxicity in rats.

Gestational exposure to paracetamol in rats induces neurofunctional alterations in the progeny

Paracetamol (PAR) is an over-the-counter medicine used as analgesic or antipyretic by 40–50% of the pregnant women in different countries. Epidemiologic studies have been associating maternal use of PAR with neurodevelopmental disruption and special attention has been given to its potential to increase the odds for neurodevelopmental disorders, such as attention-deficit hyperactive disorder and autism spectrum disorder. Population-based research do not allow the establishment of causal relationships because variable control is weak. We aimed to evaluate the potential of PAR to induce developmental neurotoxicity in rats. Pregnant Wistar rats were gavaged with PAR (350 mg/kg/day) or water from gestational day 6 until delivery. General toxicity endpoints included dams' body weight and food intake as well as pups' body weight until weaning. Behavioral evaluation occurred at post-natal days 10 (nest seeking test), 27 (behavioral stereotypy), 28 (three chamber sociability test and open field) and 29 (hot plate and elevated plus-maze). Moreover, lipid hidroperoxide (LOOH), reduced glutathione (GSH) and brain derived neurotrophic factor (BDNF) levels were quantified in prefrontal cortex and hippocampus of 22-days-old rats. Gestational exposure to PAR impaired nest seeking behavior, augmented apomorphine-induced behavioral stereotypy and decreased rostral grooming in the elevated plus maze. Exposed female pups presented elevated vertical exploration in the open field test. No alterations were observed in LOOH, GSH or BDNF levels in the prefrontal cortex or hippocampus. Exposure regimen did not affect general toxicity parameters or pups' behavior in the hot plate and sociability tests. These data suggest PAR as a developmental neurotoxicant. Observed alterations may be relevant for neurodevelopmental disorders.

Quercetin reduced the formation of N-acetyl-p-benzoquinoneimine, a toxic metabolite of paracetamol in rats and isolated rat hepatocytes.

N-acetyl-p-benzoquinoneimine (NAPQI) is toxic metabolite of paracetamol formed primarily by cytochrome P4502E1 (CYP2E1) metabolic pathway when administered at therapeutic doses or overdose. The influence of quercetin (flavonoid) on the bioactivation of paracetamol to NAPQI was investigated using rat liver microsomes and rats in vivo. Paracetamol (80mg/kg) was administered orally without or with silymarin (100mg/kg), a known inhibitor of CYP2E1, CYP3A4 and quercetin (10 and 20mg/kg) to rats for 15 consecutive days. Area under the plasma concentration-time curve (AUC0-∞ ) and the peakplasma concentration (Cmax ) of paracetamol were dose-dependently increased with quercetin (10 and 20mg/kg) compared to paracetamol control group (p<0.001). On the other hand, the AUC0-∞ and Cmax of NAPQI were decreased significantly with quercetin. The same results were observed with silymarin also. The elevated liver and kidney functional enzymes/compounds were significantly reduced by quercetin and silymarin compared to paracetamol control group. The formation of NAPQI was reduced in the incubation samples in presence of quercetin in experiment using isolated rat hepatocytes. The presentstudy results revealed that quercetin might be inhibited the CYP2E1-mediated metabolism of paracetamol; thereby decreased the formation of NAPQI and protected the liver and kidney.

Treatment with Paracetamol is not Associated with Increased Airway Sensitivity and Risk of Asthma in Rats.

Some studies have linked the use of paracetamol (PAR) with adverse effects like wheezing, exacerbation of asthma symptoms and other respiratory problems. Other studies are inconclusive or deny this correlation. This makes the association between PAR and airway hypersensitivity very controversial and still under debate. This work investigated if chronic treatment with PAR in rats could directly affect the contraction and relaxation for different stimulus in isolated airways. Rats were treated for 2 weeks with PAR (400 mg/Kg, v.o.). The blood was collected for biochemical analysis (alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBARs reaction and glutathione) and isolated tracheal rings were prepared in organ bath to measure isometric tone after contractile and relaxant stimulus. Hepatic enzymes (ALT, AST) and lipid peroxidation were increased after PAR-treatment, while glutathione was decreased. Rats do not present any alteration in airway myocytes responsiveness, either to contractile or relaxant stimulus (i.e. cholinergic agonist, membrane depolarization, Ca2+ influx across sarcolemma, internal Ca2+ release from sarcoplasmic reticulum, Ca2+ channel blocking, β-agonist and NOmediating relaxation). Despite increased oxidative stress and reduced antioxidant defense, chronic treatment with PAR does not induce airway hypersensitivity or risk of asthma in rats.

The hepatoprotective role of the aqueous extract of ginger against the harmful effects of paracetamol in rats

The hepatoprotective role of the aqueous extract of ginger against the harmful effects of paracetamol in rats

Effect of chrysin on the formation of N-acetyl-p-benzoquinoneimine, a toxic metabolite of paracetamol in rats and isolated rat hepatocytes

Paracetamol (N-acetyl-para amino phenol) is the most commonly used analgesic and antipyretic around the world. Its causes hepatotoxicity and nephrotoxicity at overdose or even at therapeutic doses. It is primarily metabolized by glucuronidation and sulfate conjugation. It is also metabolized by cytochrome-P450 system (CYP2E1, CYP1A2 and CYP 3A4), leading to the formation of N-acetyl-p-benzoquinoneimine (NAPQI). The present study was planned to investigate the influence of chrysin (known CYP2E1 and CYP3A4 inhibitor) on the bioactivation of paracetamol to NAPQI using rat liver microsomes in vitro and rats in vivo. Paracetamol (80 mg/kg) was administered orally without or with silymarin (100 mg/kg), a known CYP2E1 inhibitor and chrysin (100 and 200 mg/kg) to rats for 15 consecutive days. The area under the plasma concentration–time curve (AUC0-∞) and the peak plasma concentration (Cmax) of paracetamol were dose-dependently increased with chrysin (100 and 200 mg/kg) compared to paracetamol control group. On the other hand, the AUC0-∞ and Cmax of NAPQI were decreased significantly with chrysin (100 and 200 mg/kg). The elevated liver and kidney function markers were significantly reduced by chrysin and silymarin compared to paracetamol control group (P < 0.01). Histopathological studies of liver and kidney also well correlated with liver and kidney function tests. Chrysin also reduced the formation of NAPQI in the incubation samples of rat hepatocytes. The present study (both in vivo and in vitro) results revealed that chrysin might be inhibited the CYP2E1, CYP1A2 and CYP3A4-mediated metabolism of paracetamol; thereby decreased the formation of NAPQI and protected the liver and kidney.

Bio and phyto-chemical effect of Amphora coffeaeformis extract against hepatic injury induced by paracetamol in rats.

Paracetamol is the most commonly used analgesic-antipyretic drugs. Its excess use causes an acute hepatotoxicity. It is well known that the Bacillariophyta alga Amphora coffeaeformis is rich in many photosynthetic pigments with antioxidant activities as well as a series of biologically active substances. The current work has been designed to study thephytochemical composition of different A. coffeaeformisalgal extracts to select the most effective one. It was verified that acetone A. coffeaeformis algal extract is rich in various pigments and polyphenolic compounds (β-carotene(9.31±0.06 mg·g-1), gallic acid(28.31 µg·g-1), catechin(38.08 µg·g-1) and p-coumaric acid(38.69 µg·g-1)). The pigments and phenolic profiles in acetone extract were determined in addition to isolation of β-carotene and fucoxanthin which exhibited free radical scavenging activity by 74.80% and 69.40%, respectively. Therefore, the highest total antioxidant capacity and free radical scavenging activity were noticed with this extract. Consequently,efficiency of thisalgal extract was evaluated against hepatic intoxication induced by paracetamol in rats. The biochemical measurements (liver functions and markers of oxidative stress) were assayed. Moreover, the native protein, lipid and calcium moieties of native protein patternsin addition tocatalase (CAT); peroxidases (POX); α- and β-esterase (EST) isoenzymes and genomic DNA patterns were electrophoretically detected in liver tissues. It was found thatparacetamol caused significant (P < 0.05) elevation in serum liver functions associatedwith decline in activities of the antioxidant enzymes in that tissues. Also, it caused alterations represented electrophoretically at qualitative level from variations in the bands number and arrangement. So that, the paracetamol treated group wasnoticed with the lowest similarity index (SI). In addition, it caused abnormalities at the quantitative level through variations in quantity of normal bands. Algal extract restored all the biochemical functions to normal levels in the algal extractsimult-treated and pre-treated groups. Furthermore, it exhibited ameliorative effect against the electrophoretic alterations through restoring the absent normal bands and hiding the abnormal ones and hence increasing the SI values especially in the extractsimult-treated group. Algal extract exhibited antagonistic effect against the hepatic injury and the deleterious effects induced by paracetamol in the extractsimult-treated group.

Modulatory effects of some natural products on hepatotoxicity induced by combination of sodium valproate and paracetamol in rats.

Possible hepatoprotective effect of Curcuma longa and/or Nigella sativa against hepatotoxicity induced by coadministration of sodium valproate (SV) and paracetamol was studied. Rats were divided into 10 groups, control groups 1, 2, 3, and 4 received vehicles, C. longa (200mg/kg, p.o.), N. sativa (250mg/kg, p.o.), or both herbs for 21days, respectively. Toxicity groups 5, 6, and 7 received SV (300mg/kg, i.p.), paracetamol (1000mg/kg, p.o.) for the last 4days or both for 21days, respectively. Protection groups 8, 9, and 10 received C. longa, N. sativa, or both, respectively, 1h before the administration of both the drugs for 21days. SV and/or paracetamol significantly increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, relative liver/body weight ratio, malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and caspase-3 (Casp-3) while significantly decreased albumin, total protein, glutathione (GSH) reduced, GSH peroxidase, and superoxide dismutase (SOD). Preadministration of C. longa and/or N. sativa caused protective effect against the hepatotoxicity induced by both drugs.