Paracetamol-induced Hepatotoxicity Research Articles

Hepatoprotective agents as calcium channel blockers in paracetamol-induced and alcohol-induced hepatotoxicity models (curative method) in rats

Background It has been reported that accumulation of Ca++ ions in the cells causes depletion of mitochondrial respiration and ATP, synthesis leading to cell death. Furthermore, it has also been reported that paracetamol and alcohol produce hepatotoxicity by facilitating accumulation of excess Ca++ in hepatocytes. Ca++ channel blockers block the entry of Ca++ into the cells. Hence, the present study is planned to evaluate hepatoprotective activity of Ca++ channel blockers in the aforementioned models. Objective The aim was to study the hepatoprotective activity of three Ca++ channel blockers, namely, lercanidipine 1/4th TD (0.09 mg), ½ TD (0.18 mg) and 1TD (0.36 mg); felodipine 1/4 TD (0.045 mg), ½ TD (0.09 mg), and 1TD (0.18 mg); and isradipine ¼ TD (0.0225 mg), medium 1/2 TD (0.045 mg), and 1TD (0.09 mg), with three selected doses in paracetamol-induced and alcohol-induced hepatotoxicity in rats with curative aspects. Materials and methods The hepatoprotective activity of Ca++ channel blockers is evaluated in PCM- (2 g/kg) and ALC-(3.76 g/kg) induced hepatotoxic models in rats. The study recorded thiopental-induced sleeping time; physical parameters like liver weight and liver volume; and biochemical parameters, like alanine transaminase, aspartate aminotransferase, alkaline phosphatase, direct bilirubin, total bilirubin, albumin, and total protein, which were estimated by using a semiauto analyzer. Silymarin is used as a standard reference drug in both the paracetamol-induced and alcohol-induced hepatotoxic models. Standard drug silymarin produced a significant hepatoprotective activity. Results Ca++ channel blockers too at three different doses as mentioned before with curative aspect produced a significant hepatoprotective activity in paracetamol-induced and alcohol-induced hepatotoxic models. Ca++ channel blockers cured the hepatotoxic effects of both paracetamol and alcohol in rats and offered hepatoprotective activity. Conclusion Lercanidipine, felodipine, and isradipine exhibited a significant hepatoprotective activity in both paracetamol-induced and alcohol-induced hepatotoxic models in rats.

Hepatoprotective, Antioxidant and Cytotoxic Potential of Aloe niebuhriana Latex Extract from Yemen

The aim of this study was to quantify the total phenolic content of Aloe niebuhriana latex extract and validate its antioxidant, hepatoprotective and cytotoxic activity. The total phenolic content of the extract was estimated spectrophotometrically using Folin Ciocalteu method. The antioxidant activity of the latex extract was determined using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay. Paracetamol-induced hepatotoxicity rat model was used to evaluate the hepatoprotective activity of the extract. Cytotoxic effect of Aloe niebuhriana latex extract was screened against breast MCF-7, liver HepG2 and colon HCT-116 cancer cell lines using sulphorhodamine B assay. The extract showed high total phenolic content (245.19 mg GAE/g) and strong antioxidant activity (IC50, 19.14 μg/ml). Aloe niebuhriana extract showed significant decrease in alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, as compared to paracetamol-induced hepatotoxicity model. Hepatoprotective potential of Aloe niebuhriana latex extract was significantly (p<0.05) better than that of the control group and silymarin (100 mg/kg/day). Results of the study were well supported by the histopathological observations. Aloe niebuhriana latex extract exhibited a weak cytotoxicity effect against MCF-7, HepG2 and HCT-116 cancer cell lines. The present results provided evidence that the plant extract inhibited hepatotoxicity induced by paracetamol, which was possibly mediated via free radical scavenging and/or inhibition of free radical generation.

Investigation of Hepatoprotective Effect of Delonix Regia Leaves in Paracetamol Induced Hepatotoxicity in SD Rats

Investigation of Hepatoprotective Effect of Delonix Regia Leaves in Paracetamol Induced Hepatotoxicity in SD Rats

Phytochemistry, hepatoprotective and antioxidant activities of Euphorbia cooperi N. E. Br.

Exploring novel and effective therapies against liver damage with antioxidant activity is a point worth studying. The present study was aimed to evaluate the hepatoprotective and antioxidant activities of Euphorbia cooperi N. E. Br. aerial parts in paracetamol-induced hepatotoxicity mice and isolates its bioactive constituents. Our findings suggest for the potential antioxidant and hepatoprotective action of the n-butanol fraction of the plant as significantly (p<0.05) prevented the increased serum marker enzymes AST, ALT and bilirubin levels, decreased hepatic MDA and recovered GSH levels. Chromatographic separation of n-butanol fraction led to isolation of seven compounds namely, Gallic acid, Bervifolin carboxylic acid, Kaempferol-3-O-s-D-rutinoside, Corilagin, 3, 3'-dimethoxy ellagic acid, 3, 4, 4'-trimethoxy ellagic acid and Ellagic acid.The structure of isolated compounds was elucidated by physical and spectroscopic analysis and by comparison with the literature data. These compounds isolated for the first time from Euphorbia cooperi N. E. Br.

MRI-based preclinical discovery of DILI: A lesson from paracetamol-induced hepatotoxicity

Worldwide, drug-induced liver injury (DILI) is a major cause of hepatic failure. It is also the leading cause of withdrawal, cautionary labeling, and restricted usage of licensed drugs; therefore, European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) warn that the existing methods of assessing DILI are insufficient and that some of the translational biomarkers of hepatotoxicity must be relooked. Magnetic resonance imaging (MRI) seems to be a proper tool in elucidating the effects of DILI in both preclinical and clinical studies, providing excellent visualization of the morphology of the liver parenchyma. Therefore, herein, we propose preclinical MRI assessment of liver injury in experimental paracetamol-treated rats. Quantitative MRI clearly provides evidence of adverse effects in the liver tissue caused by a single overdose of paracetamol (1 g kg−1 and 1.5 g kg−1 b.w.). The results of the MRI were confirmed by the histopathological examination (H&E) of the rat liver specimen, however the adverse effects were not disclosed due to standard aminotransferase assays (ALT/AST) in rat blood serum. The results of our analysis demonstrate the successful application of MRI in the examination of paracetamol-induced hepatotoxicity in rats; it has a potential to serve as the early diagnostic tool for the prediction of DILI in preclinical evaluation.

Amelioration of Paracetamol-Induced Hepatotoxicity in Rat by the Administration of Chloroform extract of Argemone mexicana

Aim: The present study was undertaken to examine the effects of Chloroform extract of Argemone mexicana using the paracetamol-induced liver damage in rats as the animal model.&#x0D; Materials and methods: Chloroform extract of Argemone mexicana (100 and 200 mg/kg body weight) was administered daily in experimental animals. The hepatoprotective efficacy of Chloroform extract of Argemone mexicana (100 and 200 mg/kg) was investigated against paracetamol-induced hepatotoxicity. The levels of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), serum alkaline phosphatase (ALP), bilirubin and triglycerides were estimated. Moreover, chloroform extract of Argemone mexicana -aided antioxidant defense against hepatotoxic insult of paracetamol was measured by evaluating a number of anti-oxidative biomarkers including reduced malondialdehyde (MDA) in the serum.&#x0D; Results: Oral administration of paracetamol (500 mg/kg b.wt.) resulted in a significant elevation of liver enzymes in serum such as SGOT, SGPT, ALP, bilirubin and triglyceride levels when compared with the results in the control group. As regards oxidative stress biomarkers, there were increased tissue levels of malondialdehyde in the group treated with paracetamol. All of these results were ameliorated by co-administration of chloroform extract of Argemone mexicana.&#x0D; Conclusions: These results suggest that the protective role of Chloroform extract of Argemone mexicana in the prevention of PCM-induced hepatic toxicity in rats was associated with a decrease of oxidative stress in hepatic tissues.&#x0D; Keywords: Antihepatotoxicity; Chloroform extract of Argemone mexicana; Paracetamol

Vitamin C, omega-3 and paracetamol pharmacokinetic interactions using saliva specimens as determiners.

Background With its low side effects profile and availability as an over-the-counter drug, paracetamol has been utilized extensively worldwide as an antipyretic and analgesic agent for decades. This is associated with the increasing concern over its ease of access and/or unawareness of the consumers to this issue of paracetamol-induced hepatotoxicity. Paracetamol-induced liver injury today is a big problem where most of the researchers are interested in the possible role of the naturally available antioxidants to ameliorate hepatotoxicity through kinetic interference. So the present study was designed to evaluate the effect of vitamin C and omega-3 on the pharmacokinetic property of paracetamol. Methods Six young (average age 29) healthy volunteers participated in the study. The study included three consecutive periods, each of which preceded by overnight fasting and separated by 6 day washout periods. The first period involved the ingestion of a single paracetamol dose. The second one included the ingestion of paracetamol and vitamin C concomitantly, and the final period included paracetamol plus omega-3. Saliva samples were collected and prepared for High-performance liquid chromatography analysis. Results There was a significant increase in saliva paracetamol level after 30 min of administration when given concomitantly with vitamin C compared with the remaining groups. No significant differences in the paracetamol concentration profile between the subjects for each group were observed at 60, 90, 120 and 150 min in all treated groups. Conclusion Concurrent administration of vitamin C with paracetamol increases significantly the Cmax level (maximum measured concentration) in saliva and increases the extent of absorption and the possibility of drug-drug interaction and risk of side effects.

Comparative evaluation of biochemical effects of date palm (&lt;i&gt;Phoenix dactylifera&lt;/i&gt;) fruit extracts on paracetamol-induced hepatotoxicity in Wistar rats

The therapeutic activity of date palm extracts (Phoenix dactylifera) against paracetamol-induced hepatotoxicity was studied in rats of the Wistar strain. Forty-eight (48) Wistar rats were assigned into 8 groups equally. Group I (normal control) were given distilled water for 14 consecutive days. Group II (negative control) received paracetamol (2 g/kg). Group III were pretreated with aqueous extract (400 mg/kg) for 7 days before receiving paracetamol (2 g/kg) for 7 additional days. Group IV were pretreated with aqueous extract (400 mg/kg) for 7 consecutive days and paracetamol (2 g/kg) for 7 additional days. Group V– received 2 g/kg of paracetamol for 7days and given 400 mg/kg aqueous extract for additional 7 days. Group VI received paracetamol (2 g/kg) for 7days followed by ethanolic extract (400 mg/kg) for 7 additional days. Group VII were co-administered paracetamol (2 g/kg) and the aqueous extract (400mg/kg) for 7 days. Group VIII were co-administered paracetamol (2 g/kg) and ethanolic extract (400 mg/kg) for 7 days. To evaluate the efficacy of the extracts on paracetamol-compromised liver in Wistar rats, the enzyme activities of ALT, AST, ALP and bilirubin concentration in serum were investigated. Treatment with aqueous and ethanolic extracts at different timing significantly (p&lt;0.05) decreased paracetamol-induced elevation of serum concentrations of ALT, AST and bilirubin. Concurrent administration of the extracts with paracetamol conferred better hepatoprotection compared to the prophylactic and curative treatments. The present findings suggest a potential therapeutic use of Phoenix dactyliferia in treatment of liver diseases.Keywords: Phoenix dactylifera, hepatoxicity, extract, paracetamol

Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway.

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.

Antioxidant and hepatoprotective activity of Piper retrofractum against Paracetamol-induced hepatotoxicity in Sprague-Dawley rat

The ethanol extracts of Piper retrofractum were investigated for antioxidant and hepatoprotective activity. Hepatoprotective activity against paracetamol-induced acute hepatotoxicity was estimated in Sprague-Dawley rat. In DPPH free radical assay the root and stem extracts showed IC50 values at 133 and 91 µg/mL, respectively, while ascorbic acid at 14 µg/mL. Extracts also exhibited hydroxyl radical scavenging activity and reducing power. HPLC-DAD analysis indicated the presence of some polyphenolic compounds. Treatment of extracts significantly reduced the elevated serum levels of GPT (P < 0.01), GOT (P < 0.01) and bilirubin (P < 0.001). Both extracts restored the reduced level of total proteins and albumin. A significant increase in HDL-c but decrease in LDL-c level was observed compared to induced control. In histopathological study of liver sections, both extracts showed minimal to mild multifocal and diffuse granular degeneration and mild to moderate lobular disarray compared to control group. Results suggest that both extracts can prevent paracetamol induced hepatotoxicity.

Evaluation of Hepatoprotective Activity of Zanthoxylum armatum on Paracetamol-induced Liver Toxicity in Rats

The present study was carried out to identify phytochemical compounds and to study the hepatoprotective activity of Zanthoxylum armatum rhizome. Phytochemical analysis was carried out using standard procedures to quantify total alkaloid and phenolic contents. Hepatoprotective activity was determined using paracetamol-induced hepatotoxicity in rats. Zanthoxylum armatum extracts showed the presence of steroids, terpenoids, flavonoids, alkaloids, glycosides, phenols, oils, tannins and carbohydrates. The methanol extract has more phenolic and alkaloid contents than other extracts. The methanol extract at 500 mg/kg showed greater hepatoprotective activity with 66.87, 64.84, 67.95, 60.76 and 65.85 % protection on aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin and total protein enzyme levels of the liver, respectively. The results of the present study and previous reports indicated that phytochemical constituents variety in Zanthoxylum armatum and its' extracts possessed antioxidant, antibacterial and hepatoprotective activity.

Ameliorative potential of a traditionally used plant Fraxinus micrantha against oxidative stress and paracetamol-induced hepatotoxicity

Background: Liver disorders are one of the serious health issues. The treatment of liver disorders and their associated complications must be done with care due to the adverse effects of present-day medications. Therefore, there is an urgent need to develop effective and non-toxic herbal drugs for hepatoprotection. Objective: The objective of the present study is to investigate the hepatoprotective potential of traditionally used plant Fraxinus micrantha against paracetamol (PCM)-induced hepatotoxicity in rats. Methods: Hepatotoxicity was induced by a standardized single oral dose of paracetamol (PCM) at 3 g/kg body weight. Standard drug (silymarin 50 mg/kg) and test drugs (chloroform and methanol extracts) were administered orally to rats for 7 days. All the animals were sacrificed on the 8th day, and blood was withdrawn by retro-orbital vein puncture, collected in fresh centrifugation tubes, and centrifuged at 10,000 rpm for 10 min to separate serum for various estimations. Livers were isolated immediately for various biochemical and histopathological studies. Results: Treatment with chloroform extract (200, 400, and 800 mg/kg) and methanol extract (200 and 400 mg/kg) ameliorated the elevated levels of hepatic markers, but a significant reduction in these levels was observed by treatment with methanol extract at 800 mg/kg. In addition, treatment with chloroform and methanol extracts resulted in the amelioration of oxidative stress along with the histopathological changes. High-performance liquid chromatographic analysis of methanol extract of F. micrantha revealed the presence of various polyphenols such as rutin, naringenin, kaempferol, physicion, quercetin, and gallic acid. Conclusion: The results of the present study revealed that the observed hepatoprotective effect of methanol extract of F. micrantha may be due to the presence of various polyphenols and also provides pharmacological evidence for the use of F. micrantha bark in folk medicine for the treatment of liver diseases.

Antioxidant and Hepatoprotective activity of Ehretia laevis Roxb against paracetamol induced acute Hepatotoxicityin wistar rats

The aim of the current study is to evaluate the antioxidant activity and hepatoprotective activity of hydroalocoholic (70%) extract and ethyl acetate fraction of Ehretia laevis Roxb in wistar rats against paracetamol-induced acute hepatotoxicity. In addition, reducing the power of the extracts and their ability to scavenge free radicals were evaluated by applying 2, 2-diphenyl 2-picrylhydrazyl hydrate (DPPH) and Reducing Power Assay. The hydroalocoholic (70%) extract and its ethyl acetate fraction of Ehretia laevis displayed strong antioxidant activity. The extracts at a dose of 100 and 200 mg/kg, p.o., showed significant dose-dependent protection against paracetamol-induced changes in the serum ASAT, ALAT, ALP, and TP. The hydroalocoholic (70%) extract and its ethyl acetate fraction also showed dose-dependent protection against Paracetamol-induced changes in liver tissue such as fatty degeneration, lymphatic infiltration, and necrosis. Among the extracts tested the ethyl acetate fraction shows better activity than the Hydroalocoholic extract.

In-Vivo Antioxidant Activity of Hibiscus plantifolius Stems

Objective: Hibiscus plantifolius is a shrub with various medicinal uses and belongs to the Malvaceae family. The present study is aimed at determining in vivo antioxidant activity of MEHP using the paracetamol-induced hepatotoxicity test in rats. Methods: The animals were randomly divided into 7 experimental groups and administered with test solutions. Rats were divided into seven groups and received 10% DMSO (negative control), Paracetamol (2 gm/kg bd. wt.), Silymarin (10 mg/kg bd.wt.) or 50mg/kg MEHP (50, 150 and 300 mg/kg) orally once daily for 7 consecutive days. The oral administration of paracetamol was performed 3 hours after the last extract administration on the 7th day. The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. Results: In this study, it was observed that MEHP extract significantly (p<0.05) increased hepatic SOD and CAT activities in paracetamol-induced liver damage in rats. The antioxidant activity was exhibited due to presence of flavonoids and tannins, phenolic compounds which was present methanolic extract of Hibiscus plantifolius. Conclusion: The antioxidant activity was exhibited due to presence of flavonoids and tannins, phenolic compounds which was present methanolic extract of Hibiscus plantifolius.

Hepatoprotective Activity of Curcuma mangga Extract on Paracetamol-Induced Male Mice

This study was carried out to investigate the protective effect of ethanol extract of Curcuma mangga rhizomes on paracetamol-induced hepatotoxicity. High dose of paracetamol (1.35g/kg bw) was used to induce hepatic necrosis of mice liver. The male mice received ethanol extract of C. mangga rhizomes (100, 200 and 400 mg/kg BW) for 7 days. The hepatoprotective actvity of extract was compared to normal, positive (curcuma) and negative control. The liver function was evaluated by measuring the biochemistry parameters which include alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, histophatological study on hepatic tissue section was also carried out. The C. mangga extract displayed hepatoprotective effect except at dose of 100 mg/kg bw. The increasing of serum levels of AST and ALT were inhibited after treatment with ethanol extract at doses of 200 and 400 mg/kb bw which was comparable with normal and curcuma as postive control (p&gt;0.05). In addition, histological assessment of hepatic tissue demonstrated no liver damage, specially at dose of 400 mg/kb BW. The result indicate that ethanol extract of C. mangga rhizomes has hepatoprotective effect, especially at doses of 200 and 400 mg/kg bw .&#x0D; &#x0D; Keywords: C. mangga, rhizomes, biochemistry parameters, histopathology

Preliminary studies on therapeutic effect of ethanolic extract of Tylophora villosa leaves against paracetamol-induced hepatotoxicity in mice

This study intended to investigate the therapeutic effect of ethanolic extract of Tylophora villosa leaves (E2TL) against paracetamol (PC)-induced hepatotoxicity (PCIH) in mice (Mus musculus). PCIH were generated using daily 250 mg/kg body weight (bw) PC administration by gavage for seven days, and then daily 27.5; 55.0; 82.5; 110.0; or 220.0 mg/kg bw E2TL were treated by gavage for seven or fourteen days. Meanwhile, the controls were given solvent only in the same manner. Mortality, blood glucose, and condition (color, weight, volume) of the livers were observed on day 15 (D15). Serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SG0T) were examined on D15, D22, and D30, and then malondialdehyde (MDA) was determined on D15. Results of this study revealed that on D15, the dosage of 110.0 mg/kg bw E2TL most effectively decreased MDA due to PCIH, from 6.78 ± 1.70 μmol/L to 3.45 ± 0.43 μmol/L, approaching the control condition (2.45 ± 0.05 μmol/L). PC administration was really toxic dosage and caused 13.3 % mortality. Blood glucose, weight, and volume of the liver decreased as the effect of PC administration, and then 220.0 mg/kg bw E2TL treatment could recover the condition as well as the controls. Color of the liver indicated a similar recovery by E2TL treatment. SGPT and SG0T increased significantly by PC administration, and this PCIH facts could be recovered gradually near the controls according to the dosages (55.0; 110.0; or 220.0 mg/kg bw) and duration (seven or fourteen days) of E2TL treatment. It could be concluded that E2TL showed therapeutic effect against PCIH in M. musculus.

Composition and hepatoprotective activity of essential oils from Ethiopian thyme species (Thymus serrulatus and Thymus schimperi)

ABSTRACTThe chemical composition of six essential oils (EOs) of Thymus serrulatus and Thymus schimperi from six localities in Ethiopia, namely Ofla, Alamata, Yilmana Densa, Tarmaber, Butajira and Bale was determined. The in vivo hepatoprotective potential of three of the EOs was evaluated. GC-MS and NMR were used to determine chemical composition and GC-FID to quantify the main compounds. The number of EO components ranged from 17 to 41. The EOs were of two chemotypes with either thymol (Ofla, Alamata, Tarmaber and Bale) or carvacrol (Yilmana Densa and Butajira) being the main compound. Hepatoprotection of EOs was tested against paracetamol-induced hepatotoxicity in Wistar albino rats. Hepatoprotective properties of the oils were demonstrated by reduced serum levels of hepatic marker enzymes (AST, ALT and ALP) and normal hepatocytes structure. The most effective one was the thymol type EO from Alamata.

Investigation of Hepatoprotective Properties of the Ethanolic Extract of Careya arborea Roxb. Bark in Paracetamol Induced Hepatotoxicity in Rats

Traditional plants have been utilized to manage hepatotoxicity according to recent trends. Careya arborea (CA) has been used in folk medicine to alleviate several diseases. In the present study, ethanolic extract of Careya arborea bark has been utilized to study its efficacy on paracetamol-induced hepatotoxicity on model rats. SD Rats of either sex (150–200 gm) were divided into 5 groups containing 6 animals each. Acute hepatotoxicity was induced by paracetamol (600 mg/kg body weight) administered once daily for one week whereas the extract of the investigated plant was given orally throughout the whole experiment at 250 and 500 mg/kg body weight. Silymarin (100 mg/kg body weight) was given orally as a standard hepatoprotective drug. The degree of hepatoprotection was determined by the estimation of biochemical parameters like ALT, AST, ALP, bilirubin, total protein, albumin and globulin. The increased serum levels of hepatic marker enzymes were found in the paracetamol treated group, indicating the severity of hepatocellular damage induced by paracetamol. Treatment with CA as well as standard hepatoprotective agent silymarin attenuated the increased levels of these hepatic enzymes. Body weight was improved insignificantly by CA, whereas liver weight was recovered significantly (p<0.05). ALT, AST, ALP as well as bilirubin levels were improved very highly significantly (p<0.001) by CA at 500 mg/kg dose. Also, the total protein and albumin levels were increased significantly at the dose of 500 mg/kg. The STD drug silymarin produced very highly significant (p<0.001) effect at 100mg/kg dose. Changes in the biochemical parameters suggested that the ethanolic extract of Careya arborea bark has shown the promising hepatoprotective effect on paracetamol-induced liver damage in rats.

PROTECTIVE EFFECT OF ACORUS CALAMUS RHIZOME IN PARACETAMOL EXPOSURE INDUCED HEPATOTOXICITY IN RATS: BIOCHEMICAL AND HISTOPATHOLOGICAL STUDY

Objective: To study the hepatoprotective activity of an aqueous and alcoholic extract of Acorus calamus rhizomes against the paracetamol induced hepatotoxicity in rats.Methods: Hepatotoxicity was induced by oral administration of paracetamol and chemical parameters such as Glutathione peroxidase, Glutathione reductase, Glutathione, Catalase, lipid peroxidation and histopathological changes in liver was studied by comparing with Silymarin, a standard hepatoprotective drug.Results: Treatment of rats with aqueous and alcoholic extract of Acoruscalamus rhizome after paracetamol administration normalized the altered levels of above parameters which may comparable with Silymarin and Vit-E. The hepatoprotective activity was confirmed by histopathological examination of the liver tissue of control and treated animals.Conclusion: Based on the result it can be concluded that Acorus calamus rhizome possesses hepatoprotective effect against paracetamol-induced hepatotoxicity in rats.

Protective effect of &lt;i&gt;Parthenium hysterophorus&lt;/i&gt; against carbon tetrachloride- and paracetamol-induced hepatotoxicity in rabbits

Purpose: To investigate the possible hepatoprotective potential of Parthenium hysterophorus crude extract (Ph.Cr) against carbon tetrachloride (CCL4)- and paracetamol-induced hepatotoxicity in rabbits.Methods: Twenty rabbits were divided into five groups of four rabbits each. Group 1 served as normal control and received normal saline (5 mL/kg). Group 2 received normal saline followed by CCL4 (0.75 mL/kg p.o dose) after 1 h. Groups 3 and 4 received Ph.Cr at doses of 15 and 30 mg/kg po, respectively, for 7 days followed by one dose of CCL4, 2 h after the last extract dose (0.75 mL/kg, sc). Group 5 received silymarin as reference standard at a dose of 100 mg/kg orally for 7 days followed by one dose of CCL4 (0.75 mL/kg, sc), 2 h after the last drug dose. The effect of the extract on potassium (K+)- induced contractions in isolated rabbit jejenum was also evaluated. At the end of the study, the animals were sacrificed and their liver architecture examined microscopically.Results: Pre-treatment of rabbits with Ph.Cr reduced ALT, ALP and TB levels (p &lt; 0.05, p &lt; 0.01, p &lt; 0.001) dose dependently. Hepatoprotective data indicate that Ph.Cr markedly reduced CCL4- and paracetamol-induced toxicity by preserving the histological architecture of the liver tissue at near normal. In isolated rabbit jejunum tissue, Ph.Cr relaxed high K+ (80 Mm)-induced contractions in a concentration-dependent (0.03 - 10 mg/mL) manner like that caused by silymarin.Conclusion: In the light of the results obtained, Parthenium hysterophorous possesses hepatoprotective activity against CCL4- and paracetamol-induced hepatic damage, possibly mediated via its antioxidant and Ca++ antagonist mechanisms.Keywords: Parthenium hysterophorus, Toxins, Hepatoprotection, Ca++ antagonist, Silymarin