Induced Liver Toxicity Research Articles

Silibinin mitigates zidovudine-induced hepatocellular degenerative changes, oxidative stress and hyperlipidaemia in rats.

Prolonged zidovudine (AZT) treatment in HIV-infected and AIDS patients is shown to induce liver toxicity leading to complications. Therapeutic regimen that could encounter this adverse effect is unavailable and management of toxicity is often symptomatic or is limited to withdrawal of therapy. In the present investigation, we evaluated the alleviating properties of silibinin (SBN), a flavanolignan obtained from Silybum marianum against subacute AZT-induced hepatotoxicity and oxidative stress in rats. AZT treatment (50 mg/kg body weight (b.w.) periorally (p.o.), daily for 45 days) caused highly significant increases in alanine transaminase, alkaline phosphatase, argininosuccinic acid lyase and bilirubin in serum. Oxidative stress is shown by a highly significant increase in lipid peroxidase and total carbonyl content and decrease in catalase and protein thiols in the liver tissue. Hyperlipidaemia is indicated by highly significant increase in total lipids and free fatty acid in serum. Evaluation of liver by haematoxylin and eosin staining shows parenchymal cell enlargement, inflammatory changes and increase in sinusoidal spaces. Simultaneous treatment of SBN (100 mg/kg b.w. p.o., daily for 45 days) significantly protected the liver against hepatotoxicity, oxidative stress and hyperlipidaemia induced by AZT, and this alleviating property is attributed to hepatoprotective, membrane-stabilizing, antioxidant and free radical scavenging properties of SBN.

Evaluation of Acute Toxicity and Hepatoprotective Activity of Scrofoloso - 5 (S5) and Livome, Electro Homoeopathic Herbal Preparations against CCl4 Induced Liver Toxicity

Evaluation of Acute Toxicity and Hepatoprotective Activity of Scrofoloso - 5 (S5) and Livome, Electro Homoeopathic Herbal Preparations against CCl4 Induced Liver Toxicity

Efficacy of a traditional unani formulation Jawarish-e-Amla Sada against CCl4induced liver toxicity in Albino Wistar rats: Comparison with silymarin treatment

Background: Jawarish‑e‑Amla Sada (JAS); a polyherbal Unani formulation, is claimed as a potential hepatoprotective agent in traditional Unani medicine treatise. Aims and Objectives: Though, JAS has its composition recorded in ancient Unani texts, there have been minimal attempts to scientifically validate its hepatoprotective potential. The present work is an attempt to evaluate the hepatoprotective activity of JAS in vivo. Materials and Methods: CCl 4 intoxicated Albino Wistar rats were used to evaluate the hepatoprotective activity of JAS (0.7 g/kg and 1.0 g/kg, p.o.) and the results were compared with, silymarin. The efficacy was established on the basis of altered levels of biochemical markers and histopathological analysis of the liver tissue. Results and Discussion: Treatment with the aqueous slurry of JAS significantly reduced the level of biochemical markers in CCl 4 intoxicated rats. These findings were well-supported by the histopathological analysis of liver tissue. The effect shown by JAS was found to be at par with silymarin treatment. Conclusion: This study suggests that CCl 4 induced liver damage can be ameliorated by traditional Unani formulation JAS. This justifies the traditional claim of JAS being a hepatoprotective agent.

Potential Antifibrotic and Angiostatic Impact of Idebenone, Carnosine and Vitamin E in Nano-Sized Titanium Dioxide-Induced Liver Injury

Background/Aim: The present study investigated the in vitro and in vivo effects of individual and combined doses of idebenone, carnosine and vitamin E on ameliorating some of the biochemical indices of nano-sized titanium dioxide (n-TiO₂) in mice liver. Methods: The in vitro cytotoxic effect of nano-sized anatase TiO₂ (21 nm) on hepatic cell lines (HepG 2) was investigated. Additionally, n-TiO₂ was orally administered (150 mg/kg/day) for 2 weeks, followed by a daily intragastric gavage of the aforementioned antioxidants for 1 month. Results: n-TiO₂ induced significant cytotoxicity in hepatic cell lines and elevated the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic total antioxidant capacity (TAC) and nitrite/nitrate (NOx) levels. Meanwhile, glutathione-S-transferase (GST) activity was significantly reduced. Moreover, RT-PCR and western blot analysis showed that n-TiO₂ significantly altered the mRNA and protein expressions of transforming growth factor-beta (TGF-β1) and Smad-2, as well as vascular endothelium growth factor (VEGF). Histopathological examination of hepatic tissue reinforced these results.Conclusion: Idebenone, carnosine and vitamin E ameliorated the deviated parameters with the combination regimen demonstrating the most pronounced effect. Oxidative stress, liver fibrosis and angiogenesis may be implicated in n-TiO₂-induced liver toxicity.

Evaluation of Antibacterial action and Hepatoprotective efficiency ofSolanum nigrumleaves extract on acetaminophen induced hepatotoxicity

Solanum nigrum leaf is one of the most important greens in throughout the world. Plants are playing a vital role in hepatoprotective activity. In this present investigation we used Solanum nigrum for the antimicrobial activity and hepatoprotective activity against acetaminophen induced liver toxicity in male albino rats. The important chemical groups present in the aqueous extract canbe determined using Fourier transform infrared spectroscopy (FT-IR). Zone of inhibition in bacterial spread plate showing a antimicrobial property of the plant extract. The aqueous extract of Solanum nigrum significantly decreases the serum enzyme alanine amino transferase (ALT), asparate amino transferase (AST), triglycerides (TGL), total cholesterol (TC) and significantly increased the total protein level. Silymarin (100 mg/kg), a known hepatoprotective drug used for comparison exhibited significant activity. The morphology of liver cells clearly indicating the treatment of Solanum nigrum against acetaminophen induced liver damage near to normal cells.

Evaluation of hepatoprotective activity of Boerhaavia diffusa against carbon tetrachloride induced liver toxicity in albino rats

Background: Modern allopathic medicine has very little to offer for the treatment of liver disorders in spite of consistent effort for new drug discovery. Hence, this study was conducted to elucidate the hepatoprotective activity of aqueous extract of traditional medicinal plant Boerhaavia diffusa against carbon tetrachloride (CCl 4 ) induced toxicity in male albino rats. Methods: The hepatoprotective effect of the aqueous extracts of B. diffusa was evaluated by biochemical parameters such as serum alanine transferases (ALT), serum asparate transferases (AST), alkaline phosphatase (ALP), total serum bilirubin, and serum protein, and confirmed by histopathology of liver. The toxicant CCl 4 was used to induce hepatotoxicity and silymarin were used as control drug. The aqueous extracts of B. diffusa were administered at the doses of 250 mg/kg/day and 500 mg/kg/day orally for 4 days. One-way analysis of variance was used for the statistical analysis of data. A probability value of p<0.05 was considered as significant. Results: Administration of B. diffusa at doses 250 and 500 mg/kg orally demonstrated hepatoprotective activity by preventing the increase of ALT, AST, ALP, and serum bilirubin and also confirmed by histopathology of the liver. The results were comparable to that of silymarin ® . Conclusion: The results of this study confirmed the hepatoprotective activity of aqueous extracts of B. diffusa at doses of 250 mg/kg/and 500 mg/kg/against CCl 4 induced hepatotoxicity in rats. However, the dose adjustments may be necessary to optimize the similar hepatoprotective efficacy in clinical settings.

Hepatoprotective activity of Eclipta alba against carbon tetrachloride-induced hepatotoxicity in albino rats

Background: Despite the tremendous scientific advancement in the field of gastroenterology over the recent years, there is not even a single effective allopathic medication available for the treatment of liver disorders. Hence, the study was conducted to elucidate the hepatoprotective activity of aqueous extract of traditional medicinal plant Eclipta alba against carbon tetrachloride (CCl 4 ) induced toxicity in male albino rats. Methods: The hepatoprotective effect of the aqueous extracts of E. alba was evaluated by biochemical parameters such as serum alanine transferases (ALT), serum aspartate transferases (AST), alkaline phosphatase (ALP), total serum bilirubin, and serum protein, and confirmed by histopathology of liver. The hepatotoxic agent CCl 4 was used to induce liver toxicity and silymarin was used as a control drug. The aqueous extracts of E. alba were administered at the doses of 250 mg/kg/day and 500 mg/kg/day orally for 4 days. One-way Analysis of Variance was used for the statistical analysis of data. A probability value of p<0.05 was considered as significant. Results: E. alba administration at doses 250 mg/kg and 500 mg/kg orally demonstrated significant hepatoprotective activity by preventing the increase of ALT, AST, ALP, and serum bilirubin and also confirmed by histopathology of the liver. The results were comparable to that of silymarin. Conclusion: The results of the study confirmed the hepatoprotective activity of aqueous extracts of E. alba at doses of 250 mg/kg and 500 mg/kg against CCl 4 induced hepatotoxicity in rats. However, the dose adjustments may be necessary to optimize the similar hepatoprotective efficacy in clinical settings.

Prenatal acetaminophen induces liver toxicity in dams, reduces fetal liver stem cells, and increases airway inflammation in adult offspring

During pregnancy, acetaminophen is one of the very few medications recommended by physicians to treat fever or pain. Recent insights from epidemiological studies suggest an association between prenatal acetaminophen medication and an increased risk for development of asthma in children later in life. The underlying pathogenesis of such association is still unknown. We aimed to develop a mouse model to provide insights into the effect of prenatal acetaminophen on maternal, fetal and adult offspring's health. The toxic effect of acetaminophen was studied in mice on 1) maternal liver; mirrored by biomarkers of liver injury, centrilobular necrosis, and infiltration of granulocytes; 2) fetal liver; reflected by the frequency of hematopoietic stem cells, and 3) postnatal health; evaluated by the severity of allergic airway inflammation among offspring. We observed an increased susceptibility towards acetaminophen-induced liver damage in pregnant mice compared to virgins. Moreover, hematopoietic stem cell frequency in fetal liver declined in response to acetaminophen. Furthermore, a greater severity of airway inflammation was observed in offspring of dams upon prenatal acetaminophen treatment, identified lung infiltration by leukocytes and eosinophil infiltration into the airways. Our newly developed mouse model on prenatal use of acetaminophen reflects findings from epidemiological studies in humans. The availability of this model will allow improvement in our understanding of how acetaminophen-related hepatotoxicity is operational in pregnant individuals and how an increased risk for allergic diseases in response to prenatal acetaminophen is mediated. Such insights, once available, may change the recommendations for prenatal acetaminophen use.

Hepatotoxicity of Methanol Seed Extract of&lt;i&gt; Aframomum melegueta&lt;/i&gt; [Roscoe] K. Schum. (Grains of paradise) in Sprague-Dawley Rats

The hepatotoxic effects of the seeds of <i>Aframomum melegueta</i> (Grains of paradise), a spice were studied in Sprague-Dawley rats. Individual rat groups received sub-chronic exposure of the methanol seed extract at 300 mg/kg for 7, 14 and 21 days respectively. Liver toxicity was evaluated with assay of circulating serum aspartate aminotransferase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP), albumin, total bilirubin concentrations and histopathology of the liver of treated experimental rats. Serum levels of AST significantly (p<0.05) increased progressively in extract-treated rats compared to the control from day 7 till the termination of the study (day 21). However, serum ALT, ALP and total bilirubin levels of test rats were only significantly (p<0.05) elevated relative to the normal on days 14 and 21 of the investigation. The dose (300 mg/kg) of extract produced AST value of 55.8±3 µL<SUP>-1</SUP> while the control was 32.2±1.9 µL<SUP>-1</SUP>; and ALT value became 16.8±1.1 µL<SUP>-1</SUP> when control was 8.6±1.1 µL<SUP>-1</SUP> on day 21; Total bilirubin was 1.4±0.1 mgdL<SUP>-1</SUP> relative to control value of 0.5±0.2 mgdL<SUP>-1</SUP>. The serum albumin levels of extract-treated rats were however, comparable with that of the normal rats throughout the study period. Histopathology of the rat livers revealed mild focal necrosis of hepatocytes at day 7, moderate multifocal areas of hepatic necrosis at day 14 and severe, diffused necrosis of hepatocytes at day 21 of treatment with the extract. The results demonstrated that the methanol seed extract<i> </i>of<i> A.</i><i> melegueta</i> was potent in inducing liver toxicity at the tested dose (300 mg/kg). Maximal caution should therefore be imbibed in prolonged excessive use of the plant seeds as spice in delicacies.

Total phenolic, flavonoid contents, in-vitro antioxidant activities and hepatoprotective effect of aqueous leaf extract of Atalantia ceylanica.

BackgroundDecoction prepared from leaves of Atalantia ceylanica is used in traditional medicine in Sri Lanka for the treatment of various liver ailments since ancient times. Lyophilized powder of the water extract of A. ceylanica leaves was investigated for its phytochemical constituents, antioxidant and hepatoprotective activity in-vitro.MethodsThe total phenolic and flavonoid contents were determined using Folin Ciocalteu method and aluminium chloride colorimetric assay respectively. The antioxidant activities of the decoction were investigated using 1,1-Diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical, nitric oxide scavenging assays and ferric ion reducing power assay. Hepatotoxicity was induced on porcine liver slices with ethanol to study hepatoprotective activity. Porcine liver slices were incubated at 37°C with different concentrations of the water extract of A. ceylanica in the presence of ethanol for 2 hours. The hepatoprotective effects were quantified by the leakage of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) to the medium. Thiobarbituric acid reactive substances (TBARS) assay was performed to examine the anti-lipid peroxidation activity caused by the plant extract.ResultsThe mean ± SD (n =9) for the levels of total phenolics and flavonoids were 4.87 ± 0.89 w/w% of gallic acid equivalents and 16.48 ± 0.63 w/w% of (-)-Epigallocatechin gallate equivalents respectively. The decoction demonstrated high antioxidant activity. The mean ± SD values of EC50 were 131.2 ± 36.1, 48.4 ± 12.1, 263.5 ± 28.3 and 87.70 ± 6.06 μg/ml for DPPH, hydroxyl radical, nitric oxide scavenging assays and ferric ion reducing power assay respectively.A significant decrease (p <0.05) was observed in ALT, AST and LDH release from porcine liver slices treated with A. ceylanica extract at a concentration of 2 mg/ml in the presence of ethanol (5 M) compared to that of ethanol (5 M) treated slices. Furthermore, a reduction in lipid peroxidation was also observed in liver slices treated with the leaf extract of A. ceylanica (2 mg/ml) compared to that of ethanol induced liver toxicity (p <0.05).ConclusionsThe results suggest that aqueous extract of A. ceylanica exerts hepatoprotective activity against ethanol induced liver toxicity of porcine liver slices which can be attributed to the antioxidant properties possessed by the plant material.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-395) contains supplementary material, which is available to authorized users.

Lipidomics investigation of reversal effect of glycyrrhizin (GL) towards lithocholic acid (LCA)-induced alteration of phospholipid profiles

Context: Glycyrrhizin (GL), the major ingredient isolated from licorice, exerts multiple pharmacological activities.Objective: To elucidate the protective mechanism of GL towards lithocholic acid (LCA)-induced liver toxicity using lipidomics.Materials and methods: GL (200 mg/kg) dissolved in corn oil was treated intraperitoneally for 7 d. On the 4th day, 200 mg/kg LCA was used to treat mice (i.p., twice daily) for another 4 d. The protective role of GL towards LCA-induced liver toxicity was investigated through evaluating the liver histology and the activity of alanine transaminase (ALT). The complete lipid profile was employed using UFLC-Triple TOF MS-based lipidomics.Results: Intraperitoneal (i.p.) administration of 200 mg/kg GL can significantly protect LCA-induced liver damage, indicated by alleviated histology alteration and prevention of the ALT elevation. Lipidomics analysis can well separate the control group from LCA-treated group, and three lipid components were major contributors, including LPC 16:0, LPC 18:0, and LPC 18:2. GL treatment can significantly prevent LCA-induced reduction of these three lipid compounds, providing a new explanation for GL's protection mechanism towards LCA-induced liver toxicity.Discussion and conclusion: The recent study highlights the importance of lipidomics in elucidating the therapeutic mechanism of herbs.

Methylglyoxal Induces Mitochondrial Dysfunction and Cell Death in Liver

Degradation of glucose is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Methylglyoxal is produced during glucose degradation and the levels of methylglyoxal are increased in diabetes patients. In this study we investigated whether methylglyoxal induces mitochondrial impairment and apoptosis in HepG2 cells and induces liver toxicity in vivo. Methylglyoxal caused apoptotic cell death in HepG2 cells. Moreover, methylglyoxal significantly promoted the production of reactive oxygen species (ROS) and depleted glutathione (GSH) content. Pretreatment with antioxidants caused a marked decrease in methylglyoxal-induced apoptosis, indicating that oxidant species are involved in the apoptotic process. Methylglyoxal treatment induced mitochondrial permeability transition, which represents mitochondrial impairment. However, pretreatment with cyclosporin A, an inhibitor of the formation of the permeability transition pore, partially inhibited methylglyoxal-induced cell death. Furthermore, acute treatment of mice with methylglyoxal increased the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating liver toxicity. Collectively, our results showed that methylglyoxal increases cell death and induces liver toxicity, which results from ROS-mediated mitochondrial dysfunction and oxidative stress.

Blueberry anthocyanins ameliorate cyclophosphamide-induced liver damage in rats by reducing inflammation and apoptosis

We attempted to determine whether blueberry anthocyanins (BA) would be protective against cyclophosphamide (CTX)-induced liver injury in SD rats. CTX was injected intraperitoneally into rats to induce liver toxicity. The rats were randomly divided into four groups: a control group, a CTX group, and two groups received BA at doses of 20 and 80 mg/kg/day for 7 days (i.g.), both before and after they were administered CTX. Liver histopathology, serum liver enzymatic activities, cytokines and apoptotic parameters were evaluated. The rats that were injected with CTX incurred liver injury, evidenced by histological changes and elevated serum enzymes activities; CTX led to elevated proinflammatory cytokines, and reduced anti-inflammatory cytokine; also induced apoptosis, indicated by increased Bax and TLR4, and decreased Bcl-2 expression in western blot assay, which was further confirmed by immunohistochemistry assay with anti-Bax antibody. BA had a protective effect against CTX-induced liver damage in rats.

English

Plants are important source of medicines, especially in developing countries, where people use plant based traditional medicines for their health care. Leaves of Taraxacum officinale L. are being used against various human disorders in folk medicine since past. Current study was conducted to explore the hepatoprotective activity of methanolic leaves extract of T. officinale L. against carbontetrachloride (CCl4) induced toxicity in rats. Various concentrations of plant&nbsp; &nbsp;extracts like 150 and 300 mg/kg of body weight as well as silymarin (100 mg/kg), a standard drug, was given to experimental animals. The results of this study indicates that the methanolic leave extracts has significantly reduced (P &lt; 0.05) the level of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) which was increased&nbsp; due to induction of CCl4. It was &nbsp;also &nbsp;observed that due to CCl4 induction, the&nbsp; level of&nbsp; bilirubin, lipid profile and antioxidants enzymes was also increased, that was significantly lowered after the treatment with the leave extracts. These results revealed that the leave extracts of T. officinale L. has protective effects against CCl4 induced liver toxicity and damage. Furthermore, histopahtological results obtained during this study also supported this claim and was probably due to presence of valuable phytochemicals in the leave extracts. &nbsp; Key words: &nbsp;Medicinal plants, Taraxacum officinale, leaves extract, animals, liver enzymes.

Hepatoprotective Effect of Calotropis procera in Isoniazid and Rifampicin Induced Hepatotoxicity

Objective: In this study anti-tubercular (Anti-TB) drugs (isoniazid [INH] and rifampicin [RMP]) induced liver toxicity has been studied for the hepatoprotective effect of hydroethanolic extract of Calotropis procera (CP) fl owers in rats. Materials and Methods: Animals were divided into four groups, group A was given normal saline (1 ml/kg), group B received INH (50 mg/kg) and RMP (100 mg/kg) group C received INH (50 mg/kg), RMP (100 mg/kg) and CP (150 mg/kg) orally for 14 days. Results: Biochemical markers of liver toxicity such as aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin and tissue histology were done inall groups. Anti-TB drugs (INH 50 mg/kg and RMP 100 mg/kg) have enhanced the ALT, AST, ALP, bilirubin and histological changes in liver, whereas co-administration of anti-TB drugs with CP has reduced these levels within the normal range. Conclusion: Findings of this study showed the hepatoprotective effect of CP against INH and RMP administration to reduce the liver damage for chronic treatment.

Vitamin D and melatonin protect the cell's viability and ameliorate the CCl4 induced cytotoxicity in HepG2 and Hep3B hepatoma cell lines.

Carbon tetrachloride (CCl4) is widely used to induce liver toxicity in in vitro/in vivo models. Lipid peroxidation (LPO) begins with toxicity and affects cell viability. Recently, the beneficial effects of melatonin and Vitamin D on cell proliferation in human normal and cancer cells were found. This study was planned to evaluate antioxidant and cytoprotective activity of melatonin and Vitamin D in CCl4 induced cytotoxicity in HepG2 and Hep3B hepatoma cell lines. Based on the cytotoxicity assay, melatonin and Vitamin D were evaluated for cytotoprotective potential against CCl4 induced toxicity in HepG2 and Hep3B liver cell lines by monitoring cell viability, LPO and glutathione (GSH) level. Different dosages of CCl4 (0.1, 0.2, 0.3 and 0.4% v/v) were applied to HepG2 and Hep3B cells in order to determine the most toxic dosage of it in a time dependent manner. The same experiments were repeated with exogenously applied melatonin (MEL) and Vitamin D to groups treated with/without CCL4. Cell viability was determined with MTT measurements at the 2nd, 24th and 48th h. GSH content and Malondialdehyde levels were measured from the cell lysates. As a result, both melatonin and Vitamin D administration during CCl4 exposure protected liver cells from CCl4 induced cell damage. Increase in LPO and decrease in GSH were found in the CCl4 groups of both cells. Contrary to these results administration of MEL and Vitamin D on cells exhibited results similar to the control groups. Therefore, melatonin and Vitamin D might be a promising therapeutic agent in several toxic hepatic diseases.

The role of air pollutants in initiating liver disease.

Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants.

Development of a safety biomarker signature to detect hepatic sinusoidal dilation associated with an anti-DLL4 biotherapeutic

Context: Biomarkers of lesion-specific drug induced liver toxicity are currently lacking.Objective: To develop a biomarker signature using routine clinical pathology parameters that predict hepatic sinusoidal dilation related to anti-DLL4 biotherapeutics.Methods: Random forest and factor analysis was used to construct a signature of routine laboratory tests to detect microscopically confirmed sinusoidal dilation of the liver.Results: A biomarker signature was developed comprising two scores (S1 and S2) with area under the curve (AUC) for sinusoidal dilation prediction of 0.81, 0.85 and 0.96 in three rat studies and 0.48 and 0.81 in two monkey studies.Conclusion: A unique, two-dimensional signature of liver parameters and red blood cell parameters could detect sinusoidal dilation in multiple preclinical species.

Hepatoprotective Effect of Dill (Anethum graveolens L.) and Fennel (Foeniculum vulgare) Oil on Hepatotoxic Rats

The present study was carried out to determine the hepatoprotective effect of some herbal oils as Dill (Anethum graveolens L.) and Fennel (foeniculum vulgare) oil seeds against carbon tetrachloride (CCL4) that caused hepatotoxicity in rats. The experiment was performed on 30 adult rat that classified into two main groups, the first main group (6 rats) was kept as control (-ve) group while the second main groups (24 rat) were administered a dose of (2 mL CCL4 /kg b.wt.) twice a week for two weeks to induce chronic damage in the liver then classified into four subgroups (six rats each) as follow, one of them (6 rats) was fed on the basal diet and used as a positive control group (+ve), however, the other three subgroups were fed on basal diets and obtained orally dill oil (1 mL/kg), Fennel oil (1 mL/kg), mixture of (0.5 dill and 0.5 mL/kg fennel) oil, respectively for 4 weeks. The hepatotoxicity produced by CCL4 administration was found to be inhibited by either Dill (Anethum graveolens L.) or Fennel (foeniculum vulgare) oil or by the mixture of both Dill and Fennel oil with evidence of significant (p<0.05) decrease levels of serum AST and ALT and significantly (p<0.05) increase the level of serum total protein and albumin. Moreover, Dill and Fennel oil supplementation induced suppression of the increased ALP activity with the concurrent depletion of raised bilirubins suggests the possibility of these oils to have ability to stabilize biliary dysfunction in rat liver during hepatic injury by CCl4. On the other hand, the increase in MDA level and the decrease activity of SOD enzymes in liver induced by CCl4 suggests enhanced lipid peroxidation leading to tissue damage and failure of antioxidant defense mechanism to prevent formation of excessive free radicals. Treatment with either Dill or Fennel oil and their mixture significantly (p<0.05) reverses these changes. Also, the studied oils have hyoplipidemic effects. Hence it is likely that the mechanism of hepatoprotection of either Dill or Fennel oil is due to its antioxidant effect. Dill or Fennel oil and their mixtures have a potent hepatoprotective action against CCL4 induced liver toxicity in rats. So that, the use of Dill and Fennel oil in food formulations may be beneficial to patients who suffer from liver diseases associated with oxidative stress.

English

This study was done to investigate the hepatoprotective effect of extracts of Caesalpinia crista against carbon tetrachloride and paracetamol induced liver toxicity in albino rats. Seeds of C. crista were subjected to ethanolic and aqueous extraction. Albino rats were exposed to carbon tetrachloride (3 ml/kg rat b.w) and paracetamol (3 g/kg rat b.w) in two different protocols. Seven groups (n = 6) of animals were used in each protocol. Olive oil was used as vehicle.&nbsp; Rats treated with extracts of Caesalpinia crista exhibited a significant reduction in CCl4 and paracetamol induced increase in serum levels of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin and also caused a significant increase in serum level of total proteins which was decreased by hepato-toxic compounds used. The protective effect of these extracts was comparable with Silymarin. Ethanolic extract of C. crista was able to normalize the biochemical levels and histopathological changes which were altered due to CCl4 and paracetamol intoxication. Key words: Hepatotoxicity, Caesalpinia crista, paracetamol, CCl4.